Skip to content
2000
image of Progress in Heterocyclic Hybrids for Breast Cancer Therapy: Emerging Trends, Hybridization Techniques, Mechanistic Pathways and SAR Insights

Abstract

Introduction

Breast cancer is a widespread and life-threatening disease. While FDA-approved anti-BC drugs have improved survival rates, issues like drug resistance and adverse effects highlight the need for new therapeutic options. Molecular hybridization, a modern drug discovery strategy, combines different pharmacophores or frameworks into a single molecule to enhance pharmacological activity and improve treatment outcomes. Hybridizing two or more heterocyclic moieties has become a promising approach in anti-cancer drug discovery.

Methods

This article reviews the role of heterocyclic hybrids in BC therapy, based on literature from 1995 to 2024 available in PubMed. Key heterocyclic hybrids, pyrimidine, triazole, indole, coumarin, beta-carboline, azepine, isoquinoline, benzoxepine, and platinum-core hybrids were included.

Results

Triazole, in particular, was found to be a highly effective scaffold for BC treatment when combined with indole, pyridazinone, and steroid pharmacophores.

Discussion

The article discusses novel molecular hybridization strategies, current BC treatment options, clinical studies, key functional groups, anti-apoptotic mechanisms, and protein-ligand interactions. Structure-activity relationships are explored to highlight desirable pharmacophoric features, aiding in the development of more effective BC therapies.

Conclusion

Each heterocyclic hybrid class of BC comprises some salient features and potentials, which may be further investigated to obtain novel effective heterocyclic hybrid molecules in BC therapy.

Loading

Article metrics loading...

/content/journals/mrmc/10.2174/0113895575386481250811052953
2025-08-13
2025-09-06
Loading full text...

Full text loading...

References

  1. Kumar N M. Nukala S.K. Swamy T N. M R. Krishna T.M. Narsimha S. Benzothiazole-[1,2,3]triazolo[5,1-a]isoindoles: Synthesis, anticancer activity, bioavailability and in silico studies against Gama-Tubulin protein. J. Mol. Struct. 2022 1250 131722 10.1016/j.molstruc.2021.131722
    [Google Scholar]
  2. Disis M.L. Park K.H. Immunomodulation of breast cancer via tumor antigen specific Th1. Cancer Res. Treat. 2009 41 3 117 121 10.4143/crt.2009.41.3.117 19809560
    [Google Scholar]
  3. Nakach F.Z. Idri A. Goceri E. A comprehensive investigation of multimodal deep learning fusion strategies for breast cancer classification. Artif. Intell. Rev. 2024 57 12 327 10.1007/s10462‑024‑10984‑z
    [Google Scholar]
  4. Leo C.P. Leo C. Szucs T.D. Breast cancer drug approvals by the US FDA from 1949 to 2018. Nat. Rev. Drug Discov. 2020 19 1 11 10.1038/d41573‑019‑00201‑w
    [Google Scholar]
  5. Sodergren S.C. Copson E. White A. Efficace F. Sprangers M. Fitzsimmons D. Bottomley A. Johnson C.D. Systematic review of the side effects associated with anti-HER2-targeted therapies used in the treatment of breast cancer, on behalf of the EORTC quality of life group. Target. Oncol. 2016 11 3 277 292 10.1007/s11523‑015‑0409‑2 26677846
    [Google Scholar]
  6. Zhang Y. Yan H. Xu Z. Yang B. Luo P. He Q. Molecular basis for class side effects associated with PI3K/AKT/mTOR pathway inhibitors. Expert Opin. Drug Metab. Toxicol. 2019 15 9 767 774 10.1080/17425255.2019.1663169 31478386
    [Google Scholar]
  7. Sandhu D. Antolin A.A. Cox A.R. Jones A.M. Identification of different side effects between PARP inhibitors and their polypharmacological multi‐target rationale. Br. J. Clin. Pharmacol. 2022 88 2 742 752 10.1111/bcp.15015 34327724
    [Google Scholar]
  8. Yang L. Xue J. Yang Z. Wang M. Yang P. Dong Y. He X. Bao G. Peng S. Side effects of CDK4/6 inhibitors in the treatment of HR+/HER2− advanced breast cancer: A systematic review and meta-analysis of randomized controlled trials. Ann. Palliat. Med. 2021 10 5 5590 5599 10.21037/apm‑21‑1096 34107710
    [Google Scholar]
  9. Szumilak M. Wiktorowska-Owczarek A. Stanczak A. Hybrid drugs—a strategy for overcoming anticancer drug resistance? Molecules 2021 26 9 2601 10.3390/molecules26092601 33946916
    [Google Scholar]
  10. Kumar N. Goel N. Heterocyclic compounds: Importance in anticancer drug discovery. Anticancer. Agents Med. Chem. 2022 22 19 3196 3207 10.2174/1871520622666220404082648 35379130
    [Google Scholar]
  11. Barrett I. Meegan M.J. Hughes R.B. Carr M. Knox A.J.S. Artemenko N. Golfis G. Zisterer D.M. Lloyd D.G. Synthesis, biological evaluation, structural–activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators. Bioorg. Med. Chem. 2008 16 21 9554 9573 10.1016/j.bmc.2008.09.035 18835176
    [Google Scholar]
  12. Manda R.R. Nadh R.V. Viveka T.L. Angajala G. Aruna V. New benzylidene festooned thiazolidinone-coumarin molecular hybrids targeting Human Breast adenocarcinoma cells: Design, synthesis, SAR, molecular Modelling and biological evaluation as CDK2 inhibitors. J. Mol. Struct. 2023 1285 135453 10.1016/j.molstruc.2023.135453
    [Google Scholar]
  13. Naishima N.L. Faizan S. Raju R.M. Sruthi A.S.V.L. Ng V. Sharma G.K. Vasanth K.S. Shivaraju V.K. Ramu R. Kumar B.R.P. Design, synthesis, analysis, evaluation of cytotoxicity against MCF-7 breast cancer cells, 3D QSAR studies and EGFR, HER2 inhibition studies on novel biginelli 1,4-dihydropyrimidines. J. Mol. Struct. 2023 1277 134848 10.1016/j.molstruc.2022.134848
    [Google Scholar]
  14. Ahmed M.F. Santali E.Y. Mohi El-Deen E.M. Naguib I.A. El-Haggar R. Development of pyridazine derivatives as potential EGFR inhibitors and apoptosis inducers: Design, synthesis, anticancer evaluation, and molecular modeling studies. Bioorg. Chem. 2021 106 104473 10.1016/j.bioorg.2020.104473 33243490
    [Google Scholar]
  15. Sreenatha V. Srinivasa S.M. Rajendra Prasad K.J. Design, synthesis, bioevaluation, DFT, docking, and molecular dynamic simulation for selected novel 1,3,4-Oxadiazole - indole derivatives hybrid against estrogen receptor alpha. J. Mol. Struct. 2022 1269 133789 10.1016/j.molstruc.2022.133789
    [Google Scholar]
  16. Liu J.T. Jaunky D.B. Larocque K. Chen F. Mckibbon K. Sirouspour M. Taylor S. Shafeii A. Campbell D. Braga H. Piekny A. Forgione P. Design, structure-activity relationship study and biological evaluation of the thieno[3,2-c]isoquinoline scaffold as a potential anti-cancer agent. Bioorg. Med. Chem. Lett. 2021 52 128327 10.1016/j.bmcl.2021.128327 34416378
    [Google Scholar]
  17. Badawi W.A. Samir M. Fathy H.M. Okda T.M. Noureldin M.H. Atwa G.M.K. AboulWafa O.M. Design, synthesis and molecular docking study of new pyrimidine-based hydrazones with selective anti-proliferative activity against MCF-7 and MDA-MB-231 human breast cancer cell lines. Bioorg. Chem. 2023 138 106610 10.1016/j.bioorg.2023.106610 37210828
    [Google Scholar]
  18. Meegan M.J. Barrett I. Zimmermann J. Knox A.J.S. Zisterer D.M. Lloyd D.G. Benzothiepin-derived molecular scaffolds for estrogen receptor modulators: Synthesis and antagonistic effects in breast cancer cells. J. Enzyme Inhib. Med. Chem. 2007 22 5 655 666 10.1080/14756360701503232 18035834
    [Google Scholar]
  19. Hu X. Gao X. Gao G. Wang Y. Cao H. Li D. Hua H. Discovery of β-carboline-(phenylsulfonyl)furoxan hybrids as potential anti-breast cancer agents. Bioorg. Med. Chem. Lett. 2021 40 127952 10.1016/j.bmcl.2021.127952 33744443
    [Google Scholar]
  20. Elmegeed G.A. Yahya S.M.M. Abd-Elhalim M.M. Mohamed M.S. Mohareb R.M. Elsayed G.H. Evaluation of heterocyclic steroids and curcumin derivatives as anti-breast cancer agents: Studying the effect on apoptosis in MCF-7 breast cancer cells. Steroids 2016 115 80 89 10.1016/j.steroids.2016.08.014 27553725
    [Google Scholar]
  21. Alosaimy A.M. Abouzied A.S. Alsaedi A.M. Alafnan A. Alamri A. Alamri M.A. Discovery of novel indene-based hybrids as breast cancer inhibitors targeting Hsp90: Synthesis, bio-evaluation and molecular docking study. Arab. J. Chem. 2023 16 4 104569 10.1016/j.arabjc.2023.104569
    [Google Scholar]
  22. Abbot V. Sharma P. Dhiman S. Noolvi M.N. Patel H.M. Bhardwaj V. Small hybrid heteroaromatics: Resourceful biological tools in cancer research. RSC Advances 2017 7 45 28313 28349 10.1039/C6RA24662A
    [Google Scholar]
  23. Zhu C. Li X. Zhao B. Peng W. Li W. Fu W. Discovery of aryl-piperidine derivatives as potential antipsychotic agents using molecular hybridization strategy. Eur. J. Med. Chem. 2020 193 112214 10.1016/j.ejmech.2020.112214 32182489
    [Google Scholar]
  24. Tangutur A.D. Kumar D. Krishna K.V. Kantevari S. Microtubule targeting agents as cancer chemotherapeutics: An overview of molecular hybrids as stabilizing and destabilizing agents. Curr. Top. Med. Chem. 2017 17 22 2523 2537 28056738
    [Google Scholar]
  25. Gediya L.K. Njar V.C.O. Promise and challenges in drug discovery and development of hybrid anticancer drugs. Expert Opin. Drug Discov. 2009 4 11 1099 1111 10.1517/17460440903341705 23480431
    [Google Scholar]
  26. Singh A.K. Kumar A. Singh H. Sonawane P. Paliwal H. Thareja S. Pathak P. Grishina M. Jaremko M. Emwas A.H. Yadav J.P. Verma A. Khalilullah H. Kumar P. Concept of hybrid drugs and recent advancements in anticancer hybrids. Pharmaceuticals 2022 15 9 1071 10.3390/ph15091071 36145292
    [Google Scholar]
  27. Bérubé G. An overview of molecular hybrids in drug discovery. Expert Opin. Drug Discov. 2016 11 3 281 305 10.1517/17460441.2016.1135125 26727036
    [Google Scholar]
  28. Svartz N. Sulfasalazine: II. Some notes on the discovery and development of salazopyrin. Am. J. Gastroenterol. 1988 83 5 497 503 2896459
    [Google Scholar]
  29. Shalini K.V. Kumar V. Have molecular hybrids delivered effective anti-cancer treatments and what should future drug discovery focus on? Expert Opin. Drug Discov. 2021 16 4 335 363 10.1080/17460441.2021.1850686 33305635
    [Google Scholar]
  30. Zheng W. Zhao Y. Luo Q. Zhang Y. Wu K. Wang F. Multi-targeted anticancer agents. Curr. Top. Med. Chem. 2017 17 28 3084 3098 28685693
    [Google Scholar]
  31. Chaurasia M. Singh R. Sur S. Flora S.J.S. A review of FDA approved drugs and their formulations for the treatment of breast cancer. Front. Pharmacol. 2023 14 1184472 10.3389/fphar.2023.1184472 37576816
    [Google Scholar]
  32. Turner N.C. Oliveira M. Howell S.J. Dalenc F. Cortes J. Gomez Moreno H.L. Hu X. Jhaveri K. Krivorotko P. Loibl S. Morales Murillo S. Okera M. Park Y.H. Sohn J. Toi M. Tokunaga E. Yousef S. Zhukova L. de Bruin E.C. Grinsted L. Schiavon G. Foxley A. Rugo H.S. CAPItello-291 Study Group Capivasertib in hormone receptor–positive advanced breast cancer. N. Engl. J. Med. 2023 388 22 2058 2070 10.1056/NEJMoa2214131 37256976
    [Google Scholar]
  33. Narayan P. Prowell T.M. Gao J.J. Fernandes L.L. Li E. Jiang X. Qiu J. Fan J. Song P. Yu J. Zhang X. King-Kallimanis B.L. Chen W. Ricks T.K. Gong Y. Wang X. Windsor K. Rhieu S.Y. Geiser G. Banerjee A. Chen X. Reyes Turcu F. Chatterjee D.K. Pathak A. Seidman J. Ghosh S. Philip R. Goldberg K.B. Kluetz P.G. Tang S. Amiri-Kordestani L. Theoret M.R. Pazdur R. Beaver J.A. FDA approval summary: Alpelisib plus fulvestrant for patients with HR-positive, HER2-negative, PIK3CA-mutated, advanced or metastatic breast cancer. Clin. Cancer Res. 2021 27 7 1842 1849 10.1158/1078‑0432.CCR‑20‑3652 33168657
    [Google Scholar]
  34. Ahn H.K. Kim J.Y. Lee K.H. Kim G.M. Kang S.Y. Lee K.S. Kim J.H. Lee K.E. Lee M.H. Kim H.J. Kim H.J. Koh S.J. Park I.H. Sohn J. Kim S.B. Ahn J.S. Kim S. Cho H. Jung K.H. Im S.A. Park Y.H. Park W.Y. Shin J.H. Nam S.J. Lee J.E. Kim S.W. Choi Y.L. Yu J.H. Kim M. Kim T-Y. Oh D-Y. Kim T.Y. Lee D-W. Park C. Kim M.H. Jung H.H. Jung J.H. Ahn J.H. Kwon Y.M. Sim S.H. Kim Y.J. Kim S.H. Suh K.J. Lim J.H. Cho J.H. Lee J.I. Lim S.T. Hyun S.Y. Hong S.J. Korean Cancer Study Group (KCSG) Breast Cancer Committee Palbociclib plus endocrine therapy versus capecitabine in premenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (Young-PEARL): Overall survival analysis of a randomised, open-label, phase 2 study. Lancet Oncol. 2025 26 3 343 354 10.1016/S1470‑2045(25)00006‑3 39978378
    [Google Scholar]
  35. Finn R.S. Rugo H.S. Dieras V.C. Harbeck N. Overall survival (OS) with first-line palbociclib plus letrozole (PAL+LET) versus placebo plus letrozole (PBO+LET) in women with estrogen receptor–positive/human epidermal growth factor receptor 2–negative advanced breast cancer (ER+/HER2− ABC): Analyses from PALOMA-2. J Clin Oncol 2022 40 17_suppl LBA1003 LBA1003 10.1200/JCO.2022.40.17_suppl.LBA1003
    [Google Scholar]
  36. François-Martin H. Lardy-Cléaud A. Pistilli B. Levy C. Diéras V. Frenel J.S. Guiu S. Mouret-Reynier M.A. Mailliez A. Eymard J.C. Petit T. Ung M. Desmoulins I. Augereau P. Bachelot T. Uwer L. Debled M. Ferrero J.M. Clatot F. Goncalves A. Chevrot M. Chabaud S. Cottu P. Long-term results with everolimus in advanced hormone receptor positive breast cancer in a multicenter national real-world observational study. Cancers 2023 15 4 1191 10.3390/cancers15041191 36831532
    [Google Scholar]
  37. Borges V.F. Ferrario C. Aucoin N. Falkson C. Khan Q. Krop I. Welch S. Conlin A. Chaves J. Bedard P.L. Chamberlain M. Gray T. Vo A. Hamilton E. Tucatinib combined with ado-trastuzumab emtansine in advanced ERBB2/HER2-positive metastatic breast cancer: A phase 1b clinical trial. JAMA Oncol. 2018 4 9 1214 1220 10.1001/jamaoncol.2018.1812 29955792
    [Google Scholar]
  38. Lin N.U. Murthy R.K. Abramson V. Anders C. Bachelot T. Bedard P.L. Borges V. Cameron D. Carey L.A. Chien A.J. Curigliano G. DiGiovanna M.P. Gelmon K. Hortobagyi G. Hurvitz S.A. Krop I. Loi S. Loibl S. Mueller V. Oliveira M. Paplomata E. Pegram M. Slamon D. Zelnak A. Ramos J. Feng W. Winer E. Tucatinib vs placebo, both in combination with trastuzumab and capecitabine, for previously treated ERBB2 (HER2)-positive metastatic breast cancer in patients with brain metastases: Updated exploratory analysis of the HER2CLIMB randomized clinical trial. JAMA Oncol. 2023 9 2 197 205 10.1001/jamaoncol.2022.5610 36454580
    [Google Scholar]
  39. Agarwal N. Azad A.A. Carles J. Fay A.P. Matsubara N. Heinrich D. Szczylik C. De Giorgi U. Young Joung J. Fong P.C.C. Voog E. Jones R.J. Shore N.D. Dunshee C. Zschäbitz S. Oldenburg J. Lin X. Healy C.G. Di Santo N. Zohren F. Fizazi K. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): A randomised, placebo-controlled, phase 3 trial. Lancet 2023 402 10398 291 303 10.1016/S0140‑6736(23)01055‑3 37285865
    [Google Scholar]
  40. Hortobagyi G.N. Stemmer S.M. Burris H.A. Yap Y.S. Sonke G.S. Hart L. Campone M. Petrakova K. Winer E.P. Janni W. Conte P. Cameron D.A. André F. Arteaga C.L. Zarate J.P. Chakravartty A. Taran T. Le Gac F. Serra P. O’Shaughnessy J. Overall survival with ribociclib plus letrozole in advanced breast cancer. N. Engl. J. Med. 2022 386 10 942 950 10.1056/NEJMoa2114663 35263519
    [Google Scholar]
  41. Chan A Moy B Mansi J Ejlertsen B Holmes FA Chia S Final efficacy results of neratinib in HER2-positive hormone receptor-positive early-stage breast cancer from the phase III ExteNET trial. Clin Breast Cancer 2021 21 1 80 91 10.1016/j.clbc.2020.09.014
    [Google Scholar]
  42. Jhaveri K.L. Neven P. Casalnuovo M.L. Kim S.B. Tokunaga E. Aftimos P. Saura C. O’Shaughnessy J. Harbeck N. Carey L.A. Curigliano G. Llombart-Cussac A. Lim E. García Tinoco M.L. Sohn J. Mattar A. Zhang Q. Huang C.S. Hung C.C. Martinez Rodriguez J.L. Ruíz Borrego M. Nakamura R. Pradhan K.R. Cramer von Laue C. Barrett E. Cao S. Wang X.A. Smyth L.M. Bidard F.C. EMBER-3 Study Group Imlunestrant with or without abemaciclib in advanced breast cancer. N. Engl. J. Med. 2025 392 12 1189 1202 10.1056/NEJMoa2410858 39660834
    [Google Scholar]
  43. Geyer C.E. Jr Garber J.E. Gelber R.D. Yothers G. Taboada M. Ross L. Rastogi P. Cui K. Arahmani A. Aktan G. Armstrong A.C. Arnedos M. Balmaña J. Bergh J. Bliss J. Delaloge S. Domchek S.M. Eisen A. Elsafy F. Fein L.E. Fielding A. Ford J.M. Friedman S. Gelmon K.A. Gianni L. Gnant M. Hollingsworth S.J. Im S.A. Jager A. Jóhannsson Ó.Þ. Lakhani S.R. Janni W. Linderholm B. Liu T.W. Loman N. Korde L. Loibl S. Lucas P.C. Marmé F. Martinez de Dueñas E. McConnell R. Phillips K.A. Piccart M. Rossi G. Schmutzler R. Senkus E. Shao Z. Sharma P. Singer C.F. Španić T. Stickeler E. Toi M. Traina T.A. Viale G. Zoppoli G. Park Y.H. Yerushalmi R. Yang H. Pang D. Jung K.H. Mailliez A. Fan Z. Tennevet I. Zhang J. Nagy T. Sonke G.S. Sun Q. Parton M. Colleoni M.A. Schmidt M. Brufsky A.M. Razaq W. Kaufman B. Cameron D. Campbell C. Tutt A.N.J. Sevelda P. Haslbauer F. Penzinger M. Öhler L. Tinchon C. Greil R. Heibl S. Bartsch R. Wette V. Singer C.F. Pasterk C. Helfgott R. Pristauz-Telsnigg G. Stöger H. Weltermann A. Egle D. Thiel I. Fuchs D. Rumpold H. Strasser-Weippl K. Rautenberg B. Müller V. Schmidt M. Paepke S. Aydogdu M. Thomssen C. Rom J. Mau C. Fasching P. Göhring U-J. Kühn T. Noeding S. Kümmel S. Hackmann J. Stickeler E. Joshi A. Dewar J. Friedlander M. Phillips K-A. Antill Y. Woodward N. Abdi E. Tiley S. George M. Boadle D. Goodwin A. van der Westhuizen A. Kannourakis G. Murray N. McCarthy N. Kroep J. de Boer M. Heijns J. Jager A. Erdkamp F. Bakker S. Sonke G.S. Sami A. Mackey J. Prady C. Eisen A. Desbiens C. Patocskai E. Ferrario C. Gelmon K. Bordeleau L. Chalchal H. Niraula S. ido wolf Senkus E. Duhoux F. Randal d’Hondt Luce S. Roodenbeke D.K. Papadimitriou K. Borms M. Quaghebeur C. Jacot W. Brain E. Venat-Bouvet L. Lortholary A. Nowecki Z. Cardoso F. Hayward R. Bella S. Lazzaro M.F. Pilnik N. Fein L.E. Blajman C. Lerzo G. Varela M. Zarba J.J. Kaen D. Constanzo M.V. Tio J. Siggelkow W. Jackisch C. Grischke E.M. Zahm D. Tato-Varela S. Schmatloch S. Klare P. Stefek A. Rhiem K. Hoffmann O. Kümmel S. Deryal M. Gröll I. Ledwon P. Uleer C. Krabisch P. Potenberg J. Darsow M. Park-Simon T-W. Höffkes H-G. Emde T-O. Graffunder G. Tomé O. Forstmeyer D. Terhaag J. Salat C. Kast K. Weniger S. Schreiber C. Heinrich B. Dieterich M. Wüllner M.P. Conejero R.A. García Sáenz J.Á. Martinez L.C. Lanza A.A. Murillo S.M. Carrasco F.H. Tormo S.B. López I.Á. Delgado Mingorance J.I. Gomez E.Á. Santisteban M. Jurado J.C. Quiroga V. Borrego M.R. Martínez de Dueñas E. Alés Martínez J.E. De la Haba J. Jañez N.M. Lescure Á.R. Torres A.A. Crusades G.L. González-Santiago S. Aragones A.M. Ortega A.L. Molins A.B. Chacón López-Muñiz J.I. Jiménez M.M. Bertrán A.S. Rodríguez C. Cortijo L.G. Cretella E. Cortesi L. Ruggeri E.M. Verusio C. Gori S. Bonetti A. Mosconi A.M. Johannsson O. Jerusalem G. Neven P. Nagy T. Pinotti G. Colleoni M.A. Bernardo A. Gianni L. Bucci E. Biganzoli L. Dedes K. Novak U. Zaman K. Braybrooke J. Winter M. Rea D. Kelleher M. Barrett S. Chan S. Hickish T. Hurwitz J. Conibear J. Jegannathen A. Parton M. Tutt A. Allerton R. Borley A. Armstrong A. Copson E. Levitt N. Abraham J. Perren T. Roylance R. Ishida K. Toyama T. Masuda N. Watanabe J. Tokunaga E. Kinoshita T. Rai Y. Takada M. Yanagita Y. Nakamura R. Nakayama T. Naoi Y. Iwata H. Nakamura S. Takahashi M. Aogi K. Tsugawa K. Mukai H. Takano T. Osaki A. Sato N. Yamauchi H. Tokuda Y. Ito M. Sugimoto T. Bahadur S.W. Ganz P.A. Lu M.J. Lu M.J. Mita M.M. Waisman J. Polikoff J.A. Telli M.L. Seaward S.A. Suga J.M. Seaward S.A. Suga J.M. Durna L.N. Carney J.F. Menter A. Suga J.M. Puthillath A. Polikoff J.A. Suga J.M. Rohatgi N. Suga J.M. Polikoff J.A. Polikoff J.A. Feusner J.H. Bobolis K.A. Polikoff J.A. Eisenberg P.D. Suga J.M. Polikoff J.A. Wong D. Borges V.F. Urquhart A.T. Hofstatter E.W. Hofstatter E.W. Hofstatter E.W. McCarron E.C. Isaacs C. Herbolsheimer P. Varadarajan R. Raben A. Deveras R.A.E. Valdes-Albini F. Mahtani R.L. Mahtani R.L. Meisel J.L. Sumrall B.T. Jones C.F. Ofori S.N. Sumida K.N.M. Sumida K.N.M. Karwal M. Wilbur D.W. Singh J. Spector D.M. Schallenkamp J. Merkel D.E. Lo S.S. Khosla P.G. Cristofanilli M. Flaum L. Hoskins K.F. Cobleigh M.A. Lambiase E.A. Hahn O.M. Oliff I.A. Faller B.A. Wade J.L. Burhani N.D. Wade J.L. Gil A. Einhorn H.E. Storniolo A.M.V. Chang B.K. Kalra M. Robin E.L. Ansari B. Sharma P. Dakhil S.R. Dakhil S.R. Deming R.L. Cole J.T. Cole J.T. Cole J.T. Hanson D.S. Ochoa A.C. Cole J.T. Ochoa A.C. Garber J.E. Garber J.E. Zimbler H. Armstrong D.K. Tkaczuk K.H.R. Riseberg D.A. Armstrong D.K. O’Connor B.M. Openshaw T.H. Openshaw T.H. Openshaw T.H. Zakalik D. Vakhariya C.M. Schott A.F. Simon M.S. Doyle T.J. Al Baghdadi T. VanderWoude A. Flynn P.J. Zera R.T. Friday B.E.B. Ruddy K.J. Zera R.T. Smith R. Flynn P.J. Ademuyiwa Olabisi F. Ellis R. Carlson J.W. Carlson J.W. Marchello T B. Levine E.A. Marcom P.K. Harkness C.B. Tan A.R. Charles W.J. Kuzma C.S. Asaad S. Radford J.E. Steen P.D. Unnikrishnan M. Seeger G.R. Leu K.M.H. Copur M.S. Hauke R.J. Soori G.S. Hauke R.J. Arrick B.A. Reeder J.G. Toppmeyer D.L. Dayao Z.R. Adams S. Andreopoulou E. Allison M. Anampa Mesias J.D. Sharma R. Ramaswamy B. Gerds A.T. Shenk R.R. Gross H.M. Trehan S. Gross H.M. Gross H.M. Gross H.M. Shenk R.R. Gross H.M. Shenk R.R. Razaq W. Mansoor A.H. Hilton C.J. Brufsky A.M. Huynh C. Chowdhury N. Domchek S.M. Sigurdson E.R. Cescon T.P. Rovito M.A. DeNittis A.S. Vogel V.G. Julian T.B. Boyle L.E. Baez-Diaz L. Brescia F.J. Doster J.E. Siegel R.D. Wong L. Patel T. Nangia J.R. Jones C.A. Cannon G.M. Cannon G.M. Bear H.D. Vachhani H. Wilkinson M. Wood M.E. Wood M.E. Yan F. Sui X. van Haelst C.M. Specht J.M. Zhuo Y. Qamar R. Ryan M.L. Stockham A. Virani S. Qamar R. Gayle A.A. Qamar R. Qamar R. Jubelirer S.J. Kurian S. Salkeni M.A. Loman N. Linderholm B. Silander G. Hallbeck A-L. von Wachenfeldt Väppling A. Curtit E. Cardoso C. Braga S. Abreu M. Casa-Nova M. Nave M. Ciruelos Gil E.M. Gelpi J.B. Ortega A.F. Padró J.G. Bermejo de las Heras B. Cao M.G. Bañuelos J.C. Company J.A. Villaró G.V. Estevez L.G. Huober J. Busch S. Fehm T. Hahn A. Grafe A. Noesselt T. Dewitz T. Wagner H. Bechtner C. Weigel M. Kolberg H-C. Decker T. Thomalla J. Hesse T. Harbeck N. Jens-Uwe Blohmer J.S. Wolf Sütterlin M. Altena R. Chiu C-F. Chen S-C. Hou M-F. Chang Y-C. Chen S-H. Chen S-T. Huang C-S. Yeh D-C. Yu J-C. Tseng L-M. Chung W-P. Mailliez A. Petit T. Delaloge S. Lévy C. Dalivoust P. Extra J-M. Mouret-Reynier M-A. Hardy-Bessard A-C. Simon H. L’Haridon T. Mege A. Giacchetti S. Chakiba-Brugere C. Gratet A. Pottier V. Ferrero J-M. Tennevet I. Perrin C. Canon J-L. Joris S. Shao Z. Xu B. Jiang Z.F. Sun Q. Shen K. Pang D. Zhang J. Wang S. Yang H. Liao N. Zheng H. Fu P. Song C. Wang Y. Fan Z. Geng C. Tredan O. Landherr L. Kaufman B. Yerushalmi R. Uziely B. Conte P. Zamagni C. Bianchini G. De Laurentiis M. Tondini C. Gebbia V. Ciccarese M. Sarosiek T. Mackiewicz J. Słowińska A. Kalinka E. Huzarski T. Im S-A. Jung K.H. Sohn J.H. Kim J.H. Lee K.S. Park Y.H. Lee K.E. Chae Y.S. Cho E.K. OlympiA Clinical Trial Steering Committee and Investigators Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer. Ann. Oncol. 2022 33 12 1250 1268 10.1016/j.annonc.2022.09.159 36228963
    [Google Scholar]
  44. Medina P. Goodin S. Lapatinib: A dual inhibitor of human epidermal growth factor receptor tyrosine kinases. Clin. Ther. 2008 30 8 1426 1447 10.1016/j.clinthera.2008.08.008 18803986
    [Google Scholar]
  45. Cristofanilli M. Rugo H.S. Im S-A, Slamon DJ, Harbeck N, Bondarenko I, et al. Overall survival (OS) with palbociclib (PAL)+ fulvestrant (FUL) in women with hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2–) advanced breast cancer (ABC): Updated analyses from PALOMA-3. Wolters Kluwer Health 2021
    [Google Scholar]
  46. Gombos A. Selective oestrogen receptor degraders in breast cancer: A review and perspectives. Curr. Opin. Oncol. 2019 31 5 424 429 10.1097/CCO.0000000000000567 31335829
    [Google Scholar]
  47. Maximov P.Y. McDaniel R.E. Fernandes D.J. Bhatta P. Korostyshevskiy V.R. Curpan R.F. Jordan V.C. Pharmacological relevance of endoxifen in a laboratory simulation of breast cancer in postmenopausal patients. J. Natl. Cancer Inst. 2014 106 10 dju283 10.1093/jnci/dju283 25258390
    [Google Scholar]
  48. Garber K. Cancer anabolic metabolism inhibitors move into clinic. Nat. Biotechnol. 2016 34 8 794 795 10.1038/nbt0816‑794 27504761
    [Google Scholar]
  49. Palacios S. The future of the new selective estrogen receptor modulators. Menopause Int. 2007 13 1 27 34 10.1258/175404507780456791 17448265
    [Google Scholar]
  50. Bolognese M. Krege J.H. Utian W.H. Feldman R. Broy S. Meats D.L. Alam J. Lakshmanan M. Omizo M. Effects of arzoxifene on bone mineral density and endometrium in postmenopausal women with normal or low bone mass. J. Clin. Endocrinol. Metab. 2009 94 7 2284 2289 10.1210/jc.2008‑2143 19351734
    [Google Scholar]
  51. Baselga J. Llombart-Cussac A. Bellet M. Guillem-Porta V. Enas N. Krejcy K. Carrasco E. Kayitalire L. Kuta M. Lluch A. Vodvarka P. Kerbrat P. Namer M. Petruzelka L. Randomized, double-blind, multicenter trial comparing two doses of arzoxifene (LY353381) in hormone-sensitive advanced or metastatic breast cancer patients. Ann. Oncol. 2003 14 9 1383 1390 10.1093/annonc/mdg368 12954577
    [Google Scholar]
  52. Elkak A.E. Mokbel K. Pure antiestrogens and breast cancer. Curr. Med. Res. Opin. 2001 17 4 282 289 10.1185/0300799019117015 11922402
    [Google Scholar]
  53. Zhou Y. Zhang Y. Zhao D. Yu X. Shen X. Zhou Y. Wang S. Qiu Y. Chen Y. Zhu F. TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 52 D1 D1465 D1477 10.1093/nar/gkad751 37713619
    [Google Scholar]
  54. Martín M. Lim E. Chavez-MacGregor M. Bardia A. Wu J. Zhang Q. Nowecki Z. Cruz F.M. Safin R. Kim S.B. Schem C. Montero A.J. Khan S. Bandyopadhyay R. Moore H.M. Shivhare M. Patre M. Martinalbo J. Roncoroni L. Pérez-Moreno P.D. Sohn J. Aguil G. Alfie M. Caceres V. Lerzo G. Ostoich S. Boyle F. Lim E. Martin H. Oakman C. Cruz F.M. Franke F.A. Mattar A. Silva E.H. Tiscoski K. Chen W. Li W. Tong Z. Wang J. Wang S. Wang X. Wu J. Wu X. Yang J. Zhang Q. Emde T-O. Gaffunder G. Hielscher C. Lux M. Schem C. Welslau M. Schumacher C. Kuchuk I. Peretz T. Ryvo L. Yerushalmi R. Chae H. Chae Y.S. Im S-A. Kim H.J. Kim J.H. Kim S-B. Lee J.E. Park Y.H. Sohn J. Jarząb M. Nowaczyk M. Nowecki Z. Pienkowski T. Wojtukiewicz M. Wysocki P. Fomin E. Ganshina I. Kislov N. Kopp M. Kovalenko N. Makarova Y. Matrosova M. Orlova R. Poltoratsky A. Safin R. Zukov R. Wong A. Yap Y.S. Coccia-Portugal M. Fourie N. Khanyile R. Schoeman L. Chao T-C. Chen S-T. Chung W-P. Feng Y-H. Lin Y-C. Dejthevaporn T. Parinyanitikul N. Sathitruangsak C. Somwangprasert A. Tienchaianada P. Alacacioglu A. Algin E. Cabuk D. Demir C. Demirci U. Erdem D. Gündüz Ş. Yildirim M.E. Khan S. Schmid P. Sandri I. Oikonomidou O. Ansari T. Konstantis A. Hrybach S. Krochkin A. Lipetska O. Osinskii D. Hrybach S. Krochkin A. Lipetska O. Osinskii D. Andersen J.C. Cairo M. Cobb P. Konala V. McCune S.L. Montero A.J. Patt D.A. Sanchez-Rivera I. Strain S. Wendell K. acelERA Breast Cancer Study Investigators Giredestrant for estrogen receptor–positive, HER2-negative, previously treated advanced breast cancer: Results from the randomized, phase II acelERA breast cancer study. J. Clin. Oncol. 2024 42 18 2149 2160 10.1200/JCO.23.01500 38537155
    [Google Scholar]
  55. Davis L.E. Zhu L. Latour E. McMahon N. Nishikawa G. Choo F. Nusser K.D. Pittsenbarger J. Burch R. Park B. Mills G.B. Davis J.L. Davare M. Ryan C.W. Ribociclib in sequential combination with doxorubicin in anthracycline-naïve advanced soft-tissue sarcomas: Results of a dose-finding phase ib study. Clin. Cancer Res. 2025 OF1 OF9 10.1158/1078‑0432.CCR‑24‑4001 40343810
    [Google Scholar]
  56. Dean J.L. Thangavel C. McClendon A.K. Reed C.A. Knudsen E.S. Therapeutic CDK4/6 inhibition in breast cancer: Key mechanisms of response and failure. Oncogene 2010 29 28 4018 4032 10.1038/onc.2010.154 20473330
    [Google Scholar]
  57. Maennling A.E. Tur M.K. Niebert M. Klockenbring T. Zeppernick F. Gattenlöhner S. Meinhold-Heerlein I. Hussain A.F. Molecular targeting therapy against EGFR family in breast cancer: Progress and future potentials. Cancers 2019 11 12 1826 10.3390/cancers11121826 31756933
    [Google Scholar]
  58. Krishnamurti U. Silverman J.F. HER2 in breast cancer: A review and update. Adv. Anat. Pathol. 2014 21 2 100 107 10.1097/PAP.0000000000000015 24508693
    [Google Scholar]
  59. Cortesi L. Rugo H.S. Jackisch C. An overview of PARP inhibitors for the treatment of breast cancer. Target. Oncol. 2021 16 3 255 282 10.1007/s11523‑021‑00796‑4 33710534
    [Google Scholar]
  60. Mayer E.L. Targeting breast cancer with CDK inhibitors. Curr. Oncol. Rep. 2015 17 5 20 10.1007/s11912‑015‑0443‑3 25716100
    [Google Scholar]
  61. De Vos M. Schreiber V. Dantzer F. The diverse roles and clinical relevance of PARPs in DNA damage repair: Current state of the art. Biochem. Pharmacol. 2012 84 2 137 146 10.1016/j.bcp.2012.03.018 22469522
    [Google Scholar]
  62. Evers B. Helleday T. Jonkers J. Targeting homologous recombination repair defects in cancer. Trends Pharmacol. Sci. 2010 31 8 372 380 10.1016/j.tips.2010.06.001 20598756
    [Google Scholar]
  63. Fong P.C. Boss D.S. Yap T.A. Tutt A. Wu P. Mergui-Roelvink M. Mortimer P. Swaisland H. Lau A. O’Connor M.J. Ashworth A. Carmichael J. Kaye S.B. Schellens J.H.M. de Bono J.S. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. N. Engl. J. Med. 2009 361 2 123 134 10.1056/NEJMoa0900212 19553641
    [Google Scholar]
  64. Nakai K. Hung M-C. Yamaguchi H. A perspective on anti-EGFR therapies targeting triple-negative breast cancer. Am. J. Cancer Res. 2016 6 8 1609 1623 27648353
    [Google Scholar]
  65. Browne B. O’Brien N. Duffy M. Crown J. O’Donovan N. HER-2 signaling and inhibition in breast cancer. Curr. Cancer Drug Targets 2009 9 3 419 438 10.2174/156800909788166484 19442060
    [Google Scholar]
  66. Konecny G.E. Pegram M.D. Venkatesan N. Finn R. Yang G. Rahmeh M. Untch M. Rusnak D.W. Spehar G. Mullin R.J. Keith B.R. Gilmer T.M. Berger M. Podratz K.C. Slamon D.J. Activity of the dual kinase inhibitor lapatinib (GW572016) against HER-2-overexpressing and trastuzumab-treated breast cancer cells. Cancer Res. 2006 66 3 1630 1639 10.1158/0008‑5472.CAN‑05‑1182 16452222
    [Google Scholar]
  67. Ahmad I. Therapeutic significance of molecular hybrids for breast cancer research and treatment. RSC Med Chem 2023 14 2 218 238
    [Google Scholar]
  68. Rostom S.A.F. Ashour H.M.A. Abd El Razik H.A. Synthesis and biological evaluation of some novel polysubstituted pyrimidine derivatives as potential antimicrobial and anticancer agents. Arch. Pharm. 2009 342 5 299 310 10.1002/ardp.200800223 19415663
    [Google Scholar]
  69. De Clercq E. Antiviral drugs in current clinical use. J. Clin. Virol. 2004 30 2 115 133 10.1016/j.jcv.2004.02.009 15125867
    [Google Scholar]
  70. Reymova F. Sever B. Topalan E. Sevimli-Gur C. Can M. Tuyun A.F. Başoğlu F. Ece A. Otsuka M. Fujita M. Demirci H. Ciftci H. Design, synthesis, and mechanistic anticancer evaluation of new pyrimidine-tethered compounds. Pharmaceuticals 2025 18 2 270 10.3390/ph18020270 40006082
    [Google Scholar]
  71. Ataollahi E. Emami L. Al-Dies A.A.M. Zare F. Poustforoosh A. Emami M. Saadat F. Motamen F. Rezaei Z. Khabnadideh S. Design, synthesis, in silico studies and antiproliferative evaluation of some novel hybrids of pyrimidine-morpholine. Front Chem. 2025 13 1537261 10.3389/fchem.2025.1537261 40093994
    [Google Scholar]
  72. Abu-Melha S. Synthesis, molecular modelling, and antiproliferative activity of new thiadiazole-pyrazolotriazine and thiadiazole-pyrazolopyrimidine hybrids. Arab. J. Sci. Eng. 2024 49 1 381 401 10.1007/s13369‑023‑08137‑5
    [Google Scholar]
  73. Velidandla J.M.R. Koppula S.K. Organocatalytic [3+ 2] cycloaddition reaction: Synthesis of fully decorated sulfonyl-1, 2, 3-triazolyl pyrimidines as potent anticancer and EGFR inhibitors. Polycycl. Aromat. Compd. 2023 1 13
    [Google Scholar]
  74. Iliev I. Mavrova A. Yancheva D. Dimov S. Staneva G. Nesheva A. Tsoneva I. Nikolova B. 2-alkyl-substituted-4-amino-thieno[2,3-d]pyrimidines: Anti-proliferative properties to in vitro breast cancer models. Molecules 2023 28 17 6347 10.3390/molecules28176347 37687177
    [Google Scholar]
  75. Kim N.Y. Vishwanath D. Xi Z. Nagaraja O. Swamynayaka A. Kumar Harish K. Basappa S. Madegowda M. Pandey V. Sethi G. Lobie P.E. Ahn K.S. Basappa B. Discovery of pyrimidine- and coumarin-linked hybrid molecules as inducers of JNK phosphorylation through ROS generation in breast cancer cells. Molecules 2023 28 8 3450 10.3390/molecules28083450 37110684
    [Google Scholar]
  76. Mansour M.A. Oraby M.A. Muhammad Z.A. Lasheen D.S. Gaber H.M. Abouzid K.A.M. Identification of novel furo[2,3- d ]pyrimidine based chalcones as potent anti-breast cancer agents: Synthesis, in vitro and in vivo biological evaluation. RSC Advances 2022 12 13 8193 8201 10.1039/D2RA00889K 35424720
    [Google Scholar]
  77. Ding J. Liu T. Zeng C. Li B. Ai Y. Zhang X. Design, synthesis, and anti-breast-cancer activity evaluation of pyrrolo (pyrido)[2, 3-d] pyrimidine derivatives. J. Heterocycl. Chem. 2022 58 8-9 438 448
    [Google Scholar]
  78. Murahari M. Prakash K.V. Peters G.J. Mayur Y.C. Acridone-pyrimidine hybrids- design, synthesis, cytotoxicity studies in resistant and sensitive cancer cells and molecular docking studies. Eur. J. Med. Chem. 2017 139 961 981 10.1016/j.ejmech.2017.08.023 28886509
    [Google Scholar]
  79. Hosamani K.M. Reddy D.S. Devarajegowda H.C. Microwave-assisted synthesis of new fluorinated coumarin–pyrimidine hybrids as potent anticancer agents, their DNA cleavage and X-ray crystal studies. RSC Advances 2015 5 15 11261 11271 10.1039/C4RA12222D
    [Google Scholar]
  80. Abdelgawad M.A. Bakr R.B. Ahmad W. Al-Sanea M.M. Elshemy H.A.H. New pyrimidine-benzoxazole/benzimidazole hybrids: Synthesis, antioxidant, cytotoxic activity, in vitro cyclooxygenase and phospholipase A2-V inhibition. Bioorg. Chem. 2019 92 103218 10.1016/j.bioorg.2019.103218 31536956
    [Google Scholar]
  81. Gao F. Wang T. Xiao J. Huang G. Antibacterial activity study of 1,2,4-triazole derivatives. Eur. J. Med. Chem. 2019 173 274 281 10.1016/j.ejmech.2019.04.043 31009913
    [Google Scholar]
  82. Mamounas E.P. Bandos H. Lembersky B.C. Jeong J.H. Geyer C.E. Jr Rastogi P. Fehrenbacher L. Graham M.L. Chia S.K. Brufsky A.M. Walshe J.M. Soori G.S. Dakhil S.R. Seay T.E. Wade J.L. III McCarron E.C. Paik S. Swain S.M. Wickerham D.L. Wolmark N. Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 20 1 88 99 10.1016/S1470‑2045(18)30621‑1 30509771
    [Google Scholar]
  83. Emami L. Zare F. Khabnadideh S. Rezaei Z. Sabahi Z. Zare Gheshlaghi S. Behrouz M. Emami M. Ghobadi Z. Madadelahi Ardekani S. Barzegar F. Ebrahimi A. Sabet R. Synthesis, design, biological evaluation, and computational analysis of some novel uracil-azole derivatives as cytotoxic agents. BMC Chem. 2024 18 1 3 10.1186/s13065‑023‑01106‑x 38173035
    [Google Scholar]
  84. Torres NMP de O. New purine-triazole hybrids as potential anti-breast cancer agents: Synthesis, antiproliferative activity, and ADMET in silico study. Med. Chem. Res. 2023 32 8 1816 1831 10.1007/s00044‑023‑03115‑w
    [Google Scholar]
  85. Maghraby M.T.E. Mazyad Almutairi T. Bräse S. Salem O.I.A. Youssif B.G.M. Sheha M.M. New 1, 2, 3-triazole/1, 2, 4-triazole hybrids as aromatase inhibitors: Design, synthesis, and apoptotic antiproliferative activity. Molecules 2023 28 20 7092 10.3390/molecules28207092 37894571
    [Google Scholar]
  86. Serag W.M. Zahran F. Abdelghany Y.M. Elshaarawy R.F.M. Abdelhamid M.S. Synthesis and molecular docking of hybrids ionic azole Schiff bases as novel CDK1 inhibitors and anti-breast cancer agents: In vitro and in vivo study. J. Mol. Struct. 2021 1245 131041 10.1016/j.molstruc.2021.131041
    [Google Scholar]
  87. Eldehna W.M. El Hassab M.A. Abo-Ashour M.F. Al-Warhi T. Elaasser M.M. Safwat N.A. Suliman H. Ahmed M.F. Al-Rashood S.T. Abdel-Aziz H.A. El-Haggar R. Development of isatin-thiazolo[3,2-a]benzimidazole hybrids as novel CDK2 inhibitors with potent in vitro apoptotic anti-proliferative activity: Synthesis, biological and molecular dynamics investigations. Bioorg. Chem. 2021 110 104748 10.1016/j.bioorg.2021.104748 33684714
    [Google Scholar]
  88. Sanduja M. Gupta J. Singh H. Pagare P.P. Rana A. Uracil-coumarin based hybrid molecules as potent anti-cancer and anti-bacterial agents. J. Saudi Chem. Soc. 2020 24 2 251 266 10.1016/j.jscs.2019.12.001
    [Google Scholar]
  89. Kumari P. Mishra V.S. Narayana C. Khanna A. Chakrabarty A. Sagar R. Design and efficient synthesis of pyrazoline and isoxazole bridged indole C-glycoside hybrids as potential anticancer agents. Sci. Rep. 2020 10 1 6660 10.1038/s41598‑020‑63377‑x 32313038
    [Google Scholar]
  90. Chamduang C. Pingaew R. Prachayasittikul V. Prachayasittikul S. Ruchirawat S. Prachayasittikul V. Novel triazole-tetrahydroisoquinoline hybrids as human aromatase inhibitors. Bioorg. Chem. 2019 93 103327 10.1016/j.bioorg.2019.103327 31614285
    [Google Scholar]
  91. Bhatt P. Kumar M. Jha A. Synthesis, docking and anticancer activity of azo-linked hybrids of 1,3,4-thia-/oxadiazoles with cyclic imides. Mol. Divers. 2018 22 4 827 840 10.1007/s11030‑018‑9832‑5 29948580
    [Google Scholar]
  92. Zhang J-X Guo J-M Zhang T-T Lin H-J Qi N-S Li Z-G Antiproliferative phenothiazine hybrids as novel apoptosis inducers against MCF-7 breast cancer. Molecules 2018 23 6 1288 10.3390/molecules23061288
    [Google Scholar]
  93. Samosorn S. Bremner J.B. Ball A. Lewis K. Synthesis of functionalised 2-aryl-5-nitro-1H-indoles and their activity as bacterial NorA efflux pump inhibitors. Bioorg. Med. Chem. 2006 14 3 857 865 10.1016/j.bmc.2005.09.019 16203150
    [Google Scholar]
  94. Zeng W Han C Mohammed S Li S Song Y Sun F Indole-containing pharmaceuticals: targets, pharmacological activities, and SAR studies. RSC Med Chem 2024 15 3 788 808 10.1039/D3MD00677H
    [Google Scholar]
  95. Wan Y. Li Y. Yan C. Yan M. Tang Z. Indole: A privileged scaffold for the design of anti-cancer agents. Eur. J. Med. Chem. 2019 183 111691 10.1016/j.ejmech.2019.111691 31536895
    [Google Scholar]
  96. Andreani A. Granaiola M. Leoni A. Locatelli A. Morigi R. Rambaldi M. Synthesis and antitubercular activity of imidazo[2,1-b]thiazoles. Eur. J. Med. Chem. 2001 36 9 743 746 10.1016/S0223‑5234(01)01266‑1 11672884
    [Google Scholar]
  97. Abood R.G. Abdulhussein H.A. Abbas S. Majed A.A. Al-Khafagi A.A. Adil A. Alsalim T.A. Anti-breast cancer potential of new indole derivatives: Synthesis, in-silico study, and cytotoxicity evaluation on MCF-7 cells. J. Mol. Struct. 2025 1326 141176 10.1016/j.molstruc.2024.141176
    [Google Scholar]
  98. Kudličková Z. Michalková R. Salayová A. Ksiažek M. Vilková M. Bekešová S. Mojžiš J. Design, synthesis, and evaluation of novel indole hybrid chalcones and their antiproliferative and antioxidant activity. Molecules 2023 28 18 6583 10.3390/molecules28186583
    [Google Scholar]
  99. Mohamed H.A. Bekheit M.S. Ewies E.F. Awad H.M. Betz R. Hosten E.C. Abdel-Wahab B.F. Design of new hybrids indole/phthalimide/oxadiazole-1,2,3 triazole agents and their anticancer properties. J. Mol. Struct. 2023 1274 134415 10.1016/j.molstruc.2022.134415
    [Google Scholar]
  100. Qin J. Sun X. Ma Y. Cheng Y. Ma Q. Jing W. Qu S. Liu L. Design, synthesis and biological evaluation of novel 1,3,4,9-tetrahydropyrano[3,4-b]indoles as potential treatment of triple negative breast cancer by suppressing PI3K/AKT/mTOR pathway. Bioorg. Med. Chem. 2022 55 116594 10.1016/j.bmc.2021.116594 34990979
    [Google Scholar]
  101. Gaur A. Peerzada M.N. Khan N.S. Ali I. Azam A. Synthesis and anticancer evaluation of novel indole based arylsulfonylhydrazides against human breast cancer cells. ACS Omega 2022 7 46 42036 42043 10.1021/acsomega.2c03908 36440122
    [Google Scholar]
  102. Singla R. Gupta K.B. Upadhyay S. Dhiman M. Jaitak V. Design, synthesis and biological evaluation of novel indole-benzimidazole hybrids targeting estrogen receptor alpha (ER-α). Eur. J. Med. Chem. 2018 146 206 219 10.1016/j.ejmech.2018.01.051 29407951
    [Google Scholar]
  103. Wang M. Wu Y. Xu C. Zhao R. Huang Y. Zeng X. Chen T. Design and synthesis of 2‐(5‐phenylindol‐3‐yl)benzimidazole derivatives with antiproliferative effects towards triple‐negative breast cancer cells by activation of ROS‐mediated mitochondria dysfunction. Chem. Asian J. 2019 14 15 2648 2655 10.1002/asia.201900468 31144429
    [Google Scholar]
  104. Karadayi F.Z. Yaman M. Kisla M.M. Keskus A.G. Konu O. Ates-Alagoz Z. Design, synthesis and anticancer/antiestrogenic activities of novel indole-benzimidazoles. Bioorg. Chem. 2020 100 103929 10.1016/j.bioorg.2020.103929 32464404
    [Google Scholar]
  105. Kamal A. Nagaseshadri B. Nayak V.L. Srinivasulu V. Sathish M. Kapure J.S. Suresh Reddy C. Synthesis and biological evaluation of benzimidazole–oxindole conjugates as microtubule-targeting agents. Bioorg. Chem. 2015 63 72 84 10.1016/j.bioorg.2015.09.003 26469740
    [Google Scholar]
  106. Abyshev A.Z. Gindin V.A. Semenov E.V. Agaev E.M. Abdulla-zade A.A. Guseinov A.B. Structure and biological properties of 2H-1-benzopyran-2-one (coumarin) derivatives. Pharm. Chem. J. 2006 40 11 607 610 10.1007/s11094‑006‑0203‑7
    [Google Scholar]
  107. Zeki N.M. Mustafa Y.F. Coumarin hybrids: A sighting of their roles in drug targeting. Chem. Zvesti 2024 78 10 5753 5772 10.1007/s11696‑024‑03498‑z
    [Google Scholar]
  108. Rawat A. Vijaya Bhaskar Reddy A. Recent advances on anticancer activity of coumarin derivatives. Eur. J. Med. Chem. Rep. 2022 5 100038 10.1016/j.ejmcr.2022.100038
    [Google Scholar]
  109. Wu Y. Xu J. Liu Y. Zeng Y. Wu G. A review on anti-tumor mechanisms of coumarins. Front. Oncol. 2020 10 592853 10.3389/fonc.2020.592853 33344242
    [Google Scholar]
  110. Patagar D.N. Kusanur R. Batakurki S.R. Patra S.M. Patil N.R. Patil J.H. 8-benzimidazolyl coumarin-3-oxadiazoles – Synthesis, docking studies and Anti-proliferative evaluation against breast cancer. J. Mol. Struct. 2023 1294 136377 10.1016/j.molstruc.2023.136377
    [Google Scholar]
  111. Al-Warhi T. Abu Ali O.A. Alqahtani L.S. Abo-Elabass E. El Behery M. El-Baky A.E.A. Novel 3-Substituted 8-Methoxycoumarin derivatives as anti-breast cancer drugs. Cryst. 2023 13 7 1037 10.3390/cryst13071037
    [Google Scholar]
  112. Ahmed E.Y. Abdel Latif N.A. El-Mansy M.F. Elserwy W.S. Abdelhafez O.M. VEGFR-2 inhibiting effect and molecular modeling of newly synthesized coumarin derivatives as anti-breast cancer agents. Bioorg. Med. Chem. 2020 28 5 115328 10.1016/j.bmc.2020.115328 31992477
    [Google Scholar]
  113. Durgapal S.D. Soman S.S. Evaluation of novel coumarin-proline sulfonamide hybrids as anticancer and antidiabetic agents. Synth. Commun. 2019 49 21 1 15 10.1080/00397911.2019.1647439
    [Google Scholar]
  114. Kamath P.R. Sunil D. Ajees A.A. Pai K.S.R. Das S. Some new indole–coumarin hybrids; Synthesis, anticancer and Bcl-2 docking studies. Bioorg. Chem. 2015 63 101 109 10.1016/j.bioorg.2015.10.001 26469742
    [Google Scholar]
  115. Erşatır M. Yıldırım M. Giray E.S. Yalın S. Synthesis and antiproliferative evaluation of novel biheterocycles based on coumarin and 2-aminoselenophene-3-carbonitrile unit. Monatsh. Chem. 2020 151 4 625 636 10.1007/s00706‑020‑02573‑x
    [Google Scholar]
  116. Hartley F. The Occurrence. Extraction, Properties and Uses of the Platinum Group Metals Amsterdam, the Netherlands Elsevier 1991
    [Google Scholar]
  117. Sbovata S.M. Bettio F. Mozzon M. Bertani R. Venzo A. Benetollo F. Michelin R.A. Gandin V. Marzano C. Cisplatinum and transplatinum complexes with benzyliminoether ligands; Synthesis, characterization, structure-activity relationships, and in vitro and in vivo antitumor efficacy. J. Med. Chem. 2007 50 19 4775 4784 10.1021/jm070426p 17713897
    [Google Scholar]
  118. Wheate N.J. Walker S. Craig G.E. Oun R. The status of platinum anticancer drugs in the clinic and in clinical trials. Dalton Trans. 2010 39 35 8113 8127 10.1039/c0dt00292e 20593091
    [Google Scholar]
  119. Stehlikova K. Kostrhunova H. Kasparkova J. Brabec V. DNA bending and unwinding due to the major 1,2-GG intrastrand cross-link formed by antitumor cis-diamminedichloroplatinum(II) are flanking-base independent. Nucleic Acids Res. 2002 30 13 2894 2898 10.1093/nar/gkf405 12087174
    [Google Scholar]
  120. Farrell N. Transition metal complexes as drugs and chemotherapeutic agents. Springer Science & Business Media 2012
    [Google Scholar]
  121. Aronov O. Horowitz A.T. Gabizon A. Fuertes M.A. Pérez J.M. Gibson D. Nuclear localization signal-targeted poly(ethylene glycol) conjugates as potential carriers and nuclear localizing agents for carboplatin analogues. Bioconjug. Chem. 2004 15 4 814 823 10.1021/bc0499331 15264869
    [Google Scholar]
  122. Predarska I. Saoud M. Cepus V. Hey-Hawkins E. Kaluđerović G.N. SBA‐15 particles as carriers for a series of Platinum(IV) complexes with oxaliplatin scaffolds bearing different anti‐inflammatory drugs: Promising strategy against breast cancer. Adv. Ther. 2023 6 9 2300062 10.1002/adtp.202300062
    [Google Scholar]
  123. Kvasnica M. Rarova L. Oklestkova J. Budesinsky M. Kohout L. Synthesis and cytotoxic activities of estrone and estradiol cis-dichloroplatinum(II) complexes. Bioorg. Med. Chem. 2012 20 24 6969 6978 10.1016/j.bmc.2012.10.013 23142322
    [Google Scholar]
  124. Saha P. Descôteaux C. Brasseur K. Fortin S. Leblanc V. Parent S. Asselin É. Bérubé G. Synthesis, antiproliferative activity and estrogen receptor α affinity of novel estradiol-linked platinum(II) complex analogs to carboplatin and oxaliplatin. Potential vector complexes to target estrogen-dependent tissues. Eur. J. Med. Chem. 2012 48 385 390 10.1016/j.ejmech.2011.12.017 22209414
    [Google Scholar]
  125. Provencher-Mandeville J. Debnath C. Mandal S.K. Leblanc V. Parent S. Asselin É. Bérubé G. Design, synthesis and biological evaluation of estradiol-PEG-linked platinum(II) hybrid molecules: Comparative molecular modeling study of three distinct families of hybrids. Steroids 2011 76 1-2 94 103 10.1016/j.steroids.2010.09.004 20869376
    [Google Scholar]
  126. Provencher-Mandeville J. Descôteaux C. Mandal S.K. Leblanc V. Asselin É. Bérubé G. Synthesis of 17β-estradiol-platinum(II) hybrid molecules showing cytotoxic activity on breast cancer cell lines. Bioorg. Med. Chem. Lett. 2008 18 7 2282 2287 10.1016/j.bmcl.2008.03.005 18356047
    [Google Scholar]
  127. Descôteaux C. Leblanc V. Bélanger G. Parent S. Asselin É. Bérubé G. Improved synthesis of unique estradiol-linked platinum(II) complexes showing potent cytocidal activity and affinity for the estrogen receptor alpha and beta. Steroids 2008 73 11 1077 1089 10.1016/j.steroids.2008.04.009 18572212
    [Google Scholar]
  128. Van Themsche C. Parent S. Leblanc V. Descôteaux C. Simard A.M. Bérubé G. Asselin E. VP-128, a novel oestradiol-platinum(II) hybrid with selective anti-tumour activity towards hormone-dependent breast cancer cells in vivo. Endocr. Relat. Cancer 2009 16 4 1185 1195 10.1677/ERC‑09‑0113 19661132
    [Google Scholar]
  129. Allen J.R.F. Holmstedt B.R. The simple β-carboline alkaloids. Phytochemistry 1980 19 8 1573 1582 10.1016/S0031‑9422(00)83773‑5
    [Google Scholar]
  130. Soni JP Yeole Y Shankaraiah N β-Carboline-based molecular hybrids as anticancer agents: A brief sketch. RSC Med Chem 2021 12 5 730 750
    [Google Scholar]
  131. Guan H. Chen H. Peng W. Ma Y. Cao R. Liu X. Xu A. Design of β-carboline derivatives as DNA-targeting antitumor agents. Eur. J. Med. Chem. 2006 41 10 1167 1179 10.1016/j.ejmech.2006.05.004 16790297
    [Google Scholar]
  132. Sathish M. Kavitha B. Nayak V.L. Tangella Y. Ajitha A. Nekkanti S. Alarifi A. Shankaraiah N. Nagesh N. Kamal A. Synthesis of podophyllotoxin linked β-carboline congeners as potential anticancer agents and DNA topoisomerase II inhibitors. Eur. J. Med. Chem. 2018 144 557 571 10.1016/j.ejmech.2017.12.055 29289881
    [Google Scholar]
  133. Trujillo J.I. Meyers M.J. Anderson D.R. Hegde S. Mahoney M.W. Vernier W.F. Buchler I.P. Wu K.K. Yang S. Hartmann S.J. Reitz D.B. Novel tetrahydro-β-carboline-1-carboxylic acids as inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). Bioorg. Med. Chem. Lett. 2007 17 16 4657 4663 10.1016/j.bmcl.2007.05.070 17570666
    [Google Scholar]
  134. Hayashi K. Nagao M. Sugimura T. Interactions of norharman and harman with DNA. Nucleic Acids Res. 1977 4 11 3679 3686 10.1093/nar/4.11.3679 593881
    [Google Scholar]
  135. Huang Z. Yang Z.K. Chen S.Q. Chen J.W. Bao X.Z. Ye X.Y. Wei B. Cui Z-N. Li Y-S. Wang H. Design, synthesis of N- acyl substituted β-carboline derivatives containing 5-phenyl-2-furan moiety as potent anticancer agents. Results Chem. 2022 4 100391 10.1016/j.rechem.2022.100391
    [Google Scholar]
  136. Lata S. Saha S.T. Kaur M. Awolade P. Ebenezer O. Singh P. Tetrahydro-β-carboline-naphthalimide hybrids: Synthesis and anti-proliferative evaluation on estrogen-dependent and triple-negative breast cancer cells. Bioorg. Med. Chem. 2022 1262 133053
    [Google Scholar]
  137. Sun J. Wang J. Wang X. Hu X. Cao H. Bai J. Li D. Hua H. Design and synthesis of β-carboline derivatives with nitrogen mustard moieties against breast cancer. Bioorg. Med. Chem. 2021 45 116341 10.1016/j.bmc.2021.116341 34365102
    [Google Scholar]
  138. Sharma B. Saha S.T. Perumal S. Gu L. Ebenezer O. Singh P. Kaur M. Kumar V. Design, synthesis, antiproliferative evaluation, and molecular docking studies of N -(3-Hydroxyindole)-appended β-carbolines/tetrahydro-β-carbolines targeting triple-negative and non-triple-negative breast cancer. ACS Omega 2020 5 45 28907 28917 10.1021/acsomega.0c01226 33225121
    [Google Scholar]
  139. Sharma B. Singh A. Gu L. Saha S.T. Singh-Pillay A. Cele N. Singh P. Kaur M. Kumar V. Diastereoselective approach to rationally design tetrahydro-β-carboline–isatin conjugates as potential SERMs against breast cancer. RSC Advances 2019 9 17 9809 9819 10.1039/C9RA00744J 35520746
    [Google Scholar]
  140. Reekie T.A. Kavanagh M.E. Longworth M. Kassiou M. Synthesis of biologically active seven-membered-ring heterocycles. Synthesis 2013 3211 3227
    [Google Scholar]
  141. Dorababu A. Update of recently (2016–2020) designed azepine analogs and related heterocyclic compounds with potent pharmacological activities. Polycycl. Aromat. Compd. 2023 43 3 2250 2268 10.1080/10406638.2022.2041677
    [Google Scholar]
  142. Ali T.E. Assiri M.A. Alqahtani M.N. Shati A.A. Alfaifi M.Y. Elbehairi S.E.I. Recyclization of morpholinochromonylidene–thiazolidinone using nucleophiles: Facile synthesis, cytotoxic evaluation, apoptosis, cell cycle and molecular docking studies of a novel series of azole, azine, azepine and pyran derivatives. RSC Advances 2023 13 27 18658 18675 10.1039/D3RA02777E 37346943
    [Google Scholar]
  143. Ashram M. Habashneh A.Y. Bardaweel S. Taha M.O. A click synthesis, molecular docking and biological evaluation of 1,2,3-triazoles-benzoxazepine hybrid as potential anticancer agents. Med. Chem. Res. 2023 32 2 271 287 10.1007/s00044‑022‑03001‑x
    [Google Scholar]
  144. El Azab I.H. Elkanzi N.A.A. An efficient synthetic approach towards Benzo [b] pyrano [2, 3-e][1, 4] diazepines, and their cytotoxic activity. Molecules 2020 25 9 2051 10.3390/molecules25092051 32354014
    [Google Scholar]
  145. Malayeri S.O. Tayarani-Najaran Z. Behbahani F.S. Rashidi R. Delpazir S. Ghodsi R. Synthesis and biological evaluation of benzo[b]furo[3,4-e][1,4]diazepin-1-one derivatives as anti-cancer agents. Bioorg. Chem. 2018 80 631 638 10.1016/j.bioorg.2018.07.023 30041139
    [Google Scholar]
  146. Jaiash D.A. Belal A. Abdelgawad M.A. Abdellatif K.R. Design, synthesis and biological evaluation of new pyrroloazepines with potential and selective antitumor activity. Acta Pol. Pharm. 2016 73 2 359 368 27180428
    [Google Scholar]
  147. Kamal A. Sreekanth K. Kumar P.P. Shankaraiah N. Balakishan G. Ramaiah M.J. Pushpavalli S.N.C.V.L. Ray P. Bhadra M.P. Synthesis and potential cytotoxic activity of new phenanthrylphenol-pyrrolobenzodiazepines. Eur. J. Med. Chem. 2010 45 6 2173 2181 10.1016/j.ejmech.2010.01.054 20171761
    [Google Scholar]
  148. Plazas E. Avila M M.C. Muñoz D.R. Cuca S L.E. Natural isoquinoline alkaloids: Pharmacological features and multi-target potential for complex diseases. Pharmacol. Res. 2022 177 106126 10.1016/j.phrs.2022.106126 35151857
    [Google Scholar]
  149. Adsule S. Barve V. Chen D. Ahmed F. Dou Q.P. Padhye S. Sarkar F.H. Novel Schiff base copper complexes of quinoline-2 carboxaldehyde as proteasome inhibitors in human prostate cancer cells. J. Med. Chem. 2006 49 24 7242 7246 10.1021/jm060712l 17125278
    [Google Scholar]
  150. Shi A. Nguyen T.A. Battina S.K. Rana S. Takemoto D.J. Chiang P.K. Hua D.H. Synthesis and anti-breast cancer activities of substituted quinolines. Bioorg. Med. Chem. Lett. 2008 18 11 3364 3368 10.1016/j.bmcl.2008.04.024 18457950
    [Google Scholar]
  151. Wall M.E. Wani M.C. Cook C.E. Palmer K.H. McPhail A.T. Sim G.A. Plant antitumor agents. I. The isolation and structure of camptothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata 1, 2. J. Am. Chem. Soc. 1966 88 16 3888 3890 10.1021/ja00968a057
    [Google Scholar]
  152. Cortes J.E. Kantarjian H.M. Brümmendorf T.H. Kim D.W. Turkina A.G. Shen Z.X. Pasquini R. Khoury H.J. Arkin S. Volkert A. Besson N. Abbas R. Wang J. Leip E. Gambacorti-Passerini C. Safety and efficacy of bosutinib (SKI-606) in chronic phase Philadelphia chromosome–positive chronic myeloid leukemia patients with resistance or intolerance to imatinib. Blood 2011 118 17 4567 4576 10.1182/blood‑2011‑05‑355594 21865346
    [Google Scholar]
  153. Darwish M.I.M. Moustafa A.M. Youssef A.M. Mansour M. Yousef A.I. El Omri A. Shawki H.H. Mohamed M.F. Hassaneen H.M. Abdelhamid I.A. Oishi H. Novel Tetrahydro-[1,2,4]triazolo[3,4-a] isoquinoline chalcones suppress breast carcinoma through cell cycle arrests and apoptosis. Molecules 2023 28 8 3338 10.3390/molecules28083338 37110575
    [Google Scholar]
  154. Teli G. Sharma P. Chawla P.A. Exploring the potential of substituted 4-thiazolidinone derivatives in the treatment of breast cancer: Synthesis, biological screening and in silico studies. Polycycl. Aromat. Compd. 2023 43 7 6202 6234 10.1080/10406638.2022.2112708
    [Google Scholar]
  155. Gupta S. Bartwal G. Singh A. Tanwar J. Khurana J.M. Design, synthesis and biological evaluation of spiroisoquinoline-pyrimidine derivatives as anticancer agents against MCF-7 cancer cell lines. Results Chem. 2022 4 100386 10.1016/j.rechem.2022.100386
    [Google Scholar]
  156. Suresh Kumar R. Almansour A.I. Arumugam N. D K. Papayya Balakrishna J. Diastereoselective synthesis and anticancer potential of a small library of cage-like heterocyclic hybrids. J. King Saud Univ. Sci. 2021 33 1 101238 10.1016/j.jksus.2020.101238
    [Google Scholar]
  157. Kakhki S. Shahosseini S. Zarghi A. Design and synthesis of pyrrolo [2, 1-a] isoquinoline-based derivatives as new cytotoxic agents. Iran. J. Pharm. Res. 2016 15 4 743 751 28243270
    [Google Scholar]
  158. Wijnberg J.B.P.A. van Veldhuizen A. Swarts H.J. Frankland J.C. Field J.A. Novel monochlorinated metabolites with a 1-benzoxepin skeleton from Mycena galopus. Tetrahedron Lett. 1999 40 31 5767 5770 10.1016/S0040‑4039(99)01074‑6
    [Google Scholar]
  159. Kuntala N. Telu J.R. Anireddy J.S. Pal S. A brief overview on chemistry and biology of benzoxepine. Lett. Drug Des. Discov. 2017 14 9 1086 1098 10.2174/1570180814666161227125227
    [Google Scholar]
  160. O’Boyle N.M. Barrett I. Greene L.M. Carr M. Fayne D. Twamley B. Knox A.J.S. Keely N.O. Zisterer D.M. Meegan M.J. Lead optimization of benzoxepin-type selective estrogen receptor (ER) modulators and downregulators with subtype-specific ERα and ERβ activity. J. Med. Chem. 2018 61 2 514 534 10.1021/acs.jmedchem.6b01917 28426931
    [Google Scholar]
  161. Barrett I. Carr M. O’Boyle N. Greene L.M. Knox A.J. Lloyd D.G. Zisterer D.M. Meegan M.J. Lead identification of conformationally restricted benzoxepin type combretastatin analogs: Synthesis, antiproliferative activity, and tubulin effects. J. Enzyme Inhib. Med. Chem. 2010 25 2 180 194 10.3109/14756360903169659 20222762
    [Google Scholar]
  162. Lloyd D.G. Hughes R.B. Zisterer D.M. Williams D.C. Fattorusso C. Catalanotti B. Campiani G. Meegan M.J. Benzoxepin-derived estrogen receptor modulators: A novel molecular scaffold for the estrogen receptor. J. Med. Chem. 2004 47 23 5612 5615 10.1021/jm0495834 15509159
    [Google Scholar]
  163. Monier M. El-Mekabaty A. Abdel-Latif D. Doğru Mert B. Elattar K.M. Heterocyclic steroids: Efficient routes for annulation of pentacyclic steroidal pyrimidines. Steroids 2020 154 108548 10.1016/j.steroids.2019.108548 31805293
    [Google Scholar]
  164. Birudukota N. Mudgal M.M. Shanbhag V. Discovery and development of azasteroids as anticancer agents. Steroids 2019 152 108505 10.1016/j.steroids.2019.108505 31568765
    [Google Scholar]
  165. Ilovaisky A.I. Scherbakov A.M. Chernoburova E.I. Povarov A.A. Shchetinina M.A. Merkulova V.M. Salnikova D.I. Sorokin D.V. Bozhenko E.I. Zavarzin I.V. Terent’ev A.O. Secosteroid thiosemicarbazides and secosteroid–1,2,4-triazoles as antiproliferative agents targeting breast cancer cells: Synthesis and biological evaluation. J. Steroid Biochem. Mol. Biol. 2023 234 106386 10.1016/j.jsbmb.2023.106386 37666392
    [Google Scholar]
  166. Ilovaisky A.I. Scherbakov A.M. Merkulova V.M. Chernoburova E.I. Shchetinina M.A. Andreeva O.E. Salnikova D.I. Zavarzin I.V. Terent’ev A.O. Secosteroid–quinoline hybrids as new anticancer agents. J. Steroid Biochem. Mol. Biol. 2023 228 106245 10.1016/j.jsbmb.2022.106245 36608906
    [Google Scholar]
  167. Mustafa M. El-Kardocy A. Mostafa Y.A. Development of new hetero-steroid hybrids with antiproliferative activity against MCF-7 breast cancer cells. Monatsh. Chem. 2021 152 1 137 149 10.1007/s00706‑020‑02716‑0
    [Google Scholar]
  168. Hou Q. Lin X. Lu X. Bai C. Wei H. Luo G. Xiang H. Discovery of novel steroidal-chalcone hybrids with potent and selective activity against triple-negative breast cancer. Bioorg. Med. Chem. 2020 28 23 115763 10.1016/j.bmc.2020.115763 32992255
    [Google Scholar]
  169. Kappe C.O. Stadler A. The B iginelli dihydropyrimidine synthesis. Org Rxns. 2004 63 1 116
    [Google Scholar]
  170. Matos L.H.S. Masson F.T. Simeoni L.A. Homem-de-Mello M. Biological activity of dihydropyrimidinone (DHPM) derivatives: A systematic review. Eur. J. Med. Chem. 2018 143 1779 1789 10.1016/j.ejmech.2017.10.073 29133039
    [Google Scholar]
  171. Maliga Z. Kapoor T.M. Mitchison T.J. Evidence that monastrol is an allosteric inhibitor of the mitotic kinesin Eg5. Chem. Biol. 2002 9 9 989 996 10.1016/S1074‑5521(02)00212‑0 12323373
    [Google Scholar]
  172. Jadhav J. Juvekar A. Kurane R. Khanapure S. Salunkhe R. Rashinkar G. Remarkable anti-breast cancer activity of ferrocene tagged multi-functionalized 1,4-dihydropyrimidines. Eur. J. Med. Chem. 2013 65 232 239 10.1016/j.ejmech.2013.04.021 23711834
    [Google Scholar]
  173. Dubey S. Bhosle P.A. Pyridazinone: An important element of pharmacophore possessing broad spectrum of activity. Med. Chem. Res. 2015 24 10 3579 3598 10.1007/s00044‑015‑1398‑5
    [Google Scholar]
  174. Abdelgawad M.A. Bukhari S.N.A. Musa A. Elmowafy M. Nayl A.A. El-Ghorab A.H. Sadek Abdel-Bakky M. Omar H.A. Hadal Alotaibi N. Hassan H.M. Ghoneim M.M. Bakr R.B. Phthalazone tethered 1,2,3-triazole conjugates: In silico molecular docking studies, synthesis, in vitro antiproliferative, and kinase inhibitory activities. Bioorg. Chem. 2023 133 106404 10.1016/j.bioorg.2023.106404 36812829
    [Google Scholar]
  175. Liu X. Kou J. Xiao Z. Tian F. Hu J. Zheng P. Zhu W. Design, synthesis and biological evaluation of 6, 7-disubstituted-4-phenoxyquinoline derivatives bearing pyridazinone moiety as c-Met inhibitors. Molecules 2018 23 7 1543 10.3390/molecules23071543 29949931
    [Google Scholar]
  176. Abu Ali O.A. Abd El-Fattah W. Alfaifi M.Y. Shati A.A. Elbehairi S.E.I. Abu Almaaty A.H. Elshaarawy R.F.M. Fayad E. New Mn(III)/Fe(III) complexes with thiohydantoin-supported imidazolium ionic liquids for breast cancer therapy. Inorg. Chim. Acta 2023 551 121460 10.1016/j.ica.2023.121460
    [Google Scholar]
  177. Eldehna W.M. Al-Rashood S.T. Al-Warhi T. Eskandrani R.O. Alharbi A. El Kerdawy A.M. Novel oxindole/benzofuran hybrids as potential dual CDK2/GSK-3β inhibitors targeting breast cancer: Design, synthesis, biological evaluation, and in silico studies. J. Enzyme Inhib. Med. Chem. 2021 36 1 271 286 10.1080/14756366.2020.1862101
    [Google Scholar]
  178. Coskun D. Erkisa M. Ulukaya E. Coskun M.F. Ari F. Novel 1-(7-ethoxy-1-benzofuran-2-yl) substituted chalcone derivatives: Synthesis, characterization and anticancer activity. Eur. J. Med. Chem. 2017 136 212 222 10.1016/j.ejmech.2017.05.017 28494257
    [Google Scholar]
  179. Descôteaux C. Brasseur K. Leblanc V. Parent S. Asselin É. Bérubé G. Design of novel tyrosine-nitrogen mustard hybrid molecules active against uterine, ovarian and breast cancer cell lines. Steroids 2012 77 5 403 412 10.1016/j.steroids.2011.12.021 22227028
    [Google Scholar]
  180. Favi G. Modern strategies for heterocycle synthesis. Molecules 2020 25 11 2476 2476 10.3390/molecules25112476
    [Google Scholar]
/content/journals/mrmc/10.2174/0113895575386481250811052953
Loading
/content/journals/mrmc/10.2174/0113895575386481250811052953
Loading

Data & Media loading...


  • Article Type:
    Review Article
Keywords: heterocyclic ; inhibitory activity ; BC ; SAR analysis ; clinical trials ; Molecular hybridization
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test