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image of Benzimidazole Derivatives in Breast Cancer: Target-Specific Therapeutic Breakthroughs

Abstract

Despite ongoing advancements in drug design and developments, breast cancer remains a serious and devastating disease and is ranked as the second most common illness in women. Breast cancer rates have increased significantly during the last 40 years. This necessitates the development of novel treatment techniques. Currently, chemotherapy is the primary mode of treatment for breast cancer; however, its toxicity to normal cells and drug resistance are considered the main obstacles. Researchers are looking for novel anti-breast cancer medication classes to improve cancer therapy efficacy and survival rates. Using non-targeting medicines in a 'one-size-fits-all' strategy can harm healthy cells and may not be effective for all patients. Thus, now, the treatment of breast cancer is exploring targeted-based therapy. The tactics involved in this therapy may improve patient survival rates, but their extended usage can lead to significant side effects and medication resistance. Targeted therapy enables precision medicine by targeting particular oncogenic markers in malignancies. Because of their strong cytotoxicity against several cancer cell types, heterocyclic compounds play an important role in the development of therapeutically effective anticancer drugs. Benzimidazole derivatives have grown in favour of anti-breast cancer medicines in recent years due to their broad biological characteristics and therapeutic applications. This review provides healthcare professionals and researchers with an overview of current breakthroughs (2019-2024) in benzimidazole derivatives as breast cancer-targeted therapy, based on the perspectives of leading experts. We have illuminated the diverse and evolving landscape of hybridized benzimidazole, along with its biological targets and anti-breast cancer activity. Further, we also have compiled the various ongoing clinical trials of benzimidazole scaffolds as anti-breast cancer agents. A detailed illustration of the structure-activity connection with special emphasis is provided. The effort may help to develop potent, selective, and effective drugs to combat breast cancer.

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2025-01-07
2025-09-14

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References

  1. McGuire A. Brown J. Malone C. McLaughlin R. Kerin M. Effects of age on the detection and management of breast cancer. Cancers (Basel) 2015 7 2 908 929 10.3390/cancers7020815 26010605
    [Google Scholar]
  2. Balasubramanian R. Rolph R. Morgan C. Hamed H. Genetics of breast cancer: Management strategies and risk-reducing surgery. Br. J. Hosp. Med. (Lond.) 2019 80 12 720 725 10.12968/hmed.2019.80.12.720 31822191
    [Google Scholar]
  3. Arnold M. Morgan E. Rumgay H. Mafra A. Singh D. Laversanne M. Vignat J. Gralow J.R. Cardoso F. Siesling S. Soerjomataram I. Current and future burden of breast cancer: Global statistics for 2020 and 2040. Breast 2022 66 15 23 10.1016/j.breast.2022.08.010 36084384
    [Google Scholar]
  4. Sung H. Ferlay J. Siegel R.L. Laversanne M. Soerjomataram I. Jemal A. Bray F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2021 71 3 209 249 10.3322/caac.21660 33538338
    [Google Scholar]
  5. Teli G. Chawla P.A. Hybridization of imidazole with various heterocycles in targeting cancer: A decade’s work. ChemistrySelect 2021 6 19 4803 4836 10.1002/slct.202101038
    [Google Scholar]
  6. Kumar V. Dhawan S. Girase P.S. Awolade P. Shinde S.R. Karpoormath R. Singh P. Recent advances in chalcone-based anticancer heterocycles: A structural and molecular target perspective. Curr. Med. Chem. 2021 28 33 6805 6845 10.2174/0929867328666210322102836 33749549
    [Google Scholar]
  7. Bhatia R. Rawal R.K. Coumarin hybrids: Promising scaffolds in the treatment of breast cancer. Mini Rev. Med. Chem. 2019 19 17 1443 1458 10.2174/1389557519666190308122509 30854961
    [Google Scholar]
  8. Siegel R.L. Miller K.D. Wagle N.S. Jemal A. Cancer statistics, 2023. CA Cancer J. Clin. 2023 73 1 17 48 10.3322/caac.21763 36633525
    [Google Scholar]
  9. Pal R. Teli G. Sengupta S. Maji L. Purawarga Matada G.S. An outlook of docking analysis and structure-activity relationship of pyrimidine-based analogues as EGFR inhibitors against non-small cell lung cancer (NSCLC). J. Biomol. Struct. Dyn. 2023 ••• 1 17 37642992
    [Google Scholar]
  10. 2024 https://www.who.int/news-room/fact-sheets/detail/breast-cancer
  11. Sharmin S. Rahaman M.M. Martorell M. Sastre-Serra J. Sharifi-Rad J. Butnariu M. Bagiu I.C. Bagiu R.V. Islam M.T. Cytotoxicity of synthetic derivatives against breast cancer and multi-drug resistant breast cancer cell lines: A literature-based perspective study. Cancer Cell Int. 2021 21 1 612 10.1186/s12935‑021‑02309‑9 34801046
    [Google Scholar]
  12. 2024 https://www.nationalbreastcancer.org/breast-cancer-facts/#:~:text=In%202024%2C%20an%20estimated%20310%2C720%20women%20and,you%20know%20at%20least%20one%20person%20who
  13. Bayrakçeken E. Yaralı S. Alkan Ö. Identify risk factors affecting participation of Turkish women in mammography screening for breast cancer prevention. Breast Cancer Res. Treat. 2024 205 3 487 495 10.1007/s10549‑024‑07296‑9 38453780
    [Google Scholar]
  14. Mosquera I. Barajas C.B. Theriault H. Benitez Majano S. Zhang L. Maza M. Luciani S. Carvalho A.L. Basu P. Assessment of barriers to cancer screening and interventions implemented to overcome these barriers in 27 Latin American and Caribbean countries. Int. J. Cancer 2024 155 4 719 730 10.1002/ijc.34950 38648380
    [Google Scholar]
  15. Wada K. Nagata C. Utada M. Sakata R. Kimura T. Tamakoshi A. Sugawara Y. Tsuji I. Sato R. Sawada N. Tsugane S. Oze I. Ito H. Kitamura T. Koyanagi Y.N. Lin Y. Matsuo K. Abe S.K. Inoue M. Inoue M. Abe S.K. Sawada N. Tanaka S. Kimura T. Sugawara Y. Mizoue T. Nomura S. Takimoto H. Ito H. Matsuo K. Lin Y. Wada K. Kitamura T. Sakata R. Tanaka K. Charvat H. Hidaka A. Hirabayashi M. Iwasaki M. Kitamura Y. Mori N. Muto M. Nagata C. Naito M. Nakayama T. Nishino Y. Sadakane A. Saito E. Sasazuki S. Shimazu T. Shimizu H. Sugiyama K. Suzuki H. Tamakoshi A. Tsubono Y. Tsuji I. Tsugane S. Utada M. Wakai K. Yamagiwa Y. Yamaji T. Active and passive smoking and breast cancer in Japan: A pooled analysis of nine population-based cohort studies. Int. J. Epidemiol. 2024 53 3 dyae047 10.1093/ije/dyae047 38604675
    [Google Scholar]
  16. Elkaeed E.B. Salam H.A.A.E. Sabt A. Al-Ansary G.H. Eldehna W.M. Recent advancements in the development of anti-breast cancer synthetic small molecules. Molecules 2021 26 24 7611 10.3390/molecules26247611 34946704
    [Google Scholar]
  17. Mitra S. MicroRNA therapeutics in triple negative breast cancer Arch Pathol Clin Res 2017 1 1 009 017 10.29328/journal.hjpcr.1001003
    [Google Scholar]
  18. Callahan R. Hurvitz S. Human epidermal growth factor receptor-2-positive breast cancer: Current management of early, advanced, and recurrent disease. Curr. Opin. Obstet. Gynecol. 2011 23 1 37 43 10.1097/GCO.0b013e3283414e87 21500375
    [Google Scholar]
  19. Cao L. Niu Y. Triple negative breast cancer: Special histological types and emerging therapeutic methods. Cancer Biol. Med. 2020 17 2 293 306 10.20892/j.issn.2095‑3941.2019.0465 32587770
    [Google Scholar]
  20. Schlotter C.M. Vogt U. Allgayer H. Brandt B. Molecular targeted therapies for breast cancer treatment. Breast Cancer Res. 2008 10 4 211 10.1186/bcr2112 18671839
    [Google Scholar]
  21. Shah U. Patel N. Patel M. Rohit S. Solanki N. Patel A. Patel S. Patel V. Patel R. Jawarkar R.D. Computational exploration of naturally occurring flavonoids as TGF‐β inhibitors in breast cancer: Insights from docking and molecular dynamics simulations and In‐vitro Cytotoxicity study. Chem. Biodivers. 2024 21 6 e202301903 10.1002/cbdv.202301903 38623839
    [Google Scholar]
  22. Shah U Patel A Patel S Patel M Patel A Patel S Role of natural and synthetic flavonoids as potential aromatase inhibitors in breast cancer: Structure-activity relationship perspective Anticancer Agents Med Chem 2022 22 11 2063 2079 10.2174/1871520621666211026101252
    [Google Scholar]
  23. Shah U Patel S Patel M Jain N Pandey N Chauhan A In vitro cytotoxicity and Aromatase inhibitory activity of flavonoids: Synthesis, molecular docking and in silico ADME prediction Anticancer Agents Med Chem 2022 22 7 1370 1385
    [Google Scholar]
  24. Hodson R. Precision medicine Nature 2016 537 7619 S49
    [Google Scholar]
  25. Shagufta Ahmad I. Therapeutic significance of molecular hybrids for breast cancer research and treatment. RSC Med. Chem. 2023 14 2 218 238 10.1039/D2MD00356B 36846377
    [Google Scholar]
  26. Liu J. Ming B. Gong G.H. Wang D. Bao G.L. Yu L.J. Current research on anti-breast cancer synthetic compounds. RSC Advances 2018 8 8 4386 4416 10.1039/C7RA12912B
    [Google Scholar]
  27. Liu T. Song S. Wang X. Hao J. Small-molecule inhibitors of breast cancer-related targets: Potential therapeutic agents for breast cancer. Eur. J. Med. Chem. 2021 210 112954 10.1016/j.ejmech.2020.112954 33158576
    [Google Scholar]
  28. Tantawy M.A. Nafie M.S. Elmegeed G.A. Ali I.A.I. Auspicious role of the steroidal heterocyclic derivatives as a platform for anti-cancer drugs. Bioorg. Chem. 2017 73 128 146 10.1016/j.bioorg.2017.06.006 28668650
    [Google Scholar]
  29. Pal R. Teli G. Swamy Purawarga Matada G. Sanjay Dhiwar P. nitrogen‐containing Heterocyclic scaffolds as EGFR inhibitors: Design approaches, molecular docking, and structure‐activity relationships. ChemistrySelect 2023 8 26 e202301200 10.1002/slct.202301200
    [Google Scholar]
  30. Teli G. Pal R. Maji L. Sengupta S. Raghavendra N.M. Matada G.S.P. Medicinal chemistry perspectives on recent advances in Src Kinase inhibitors as a potential target for the development of anticancer agents: Biological profile, selectivity, structure‐activity relationship. Chem. Biodivers. 2023 20 9 e202300515 10.1002/cbdv.202300515 37563848
    [Google Scholar]
  31. Singh K. Pal R. Khan S.A. Kumar B. Akhtar M.J. Insights into the structure activity relationship of nitrogen-containing heterocyclics for the development of antidepressant compounds: An updated review. J. Mol. Struct. 2021 1237 130369 10.1016/j.molstruc.2021.130369
    [Google Scholar]
  32. Salahuddin Shaharyar M. Mazumder A. Benzimidazoles: A biologically active compounds. Arab. J. Chem. 2017 10 S157 S173 10.1016/j.arabjc.2012.07.017
    [Google Scholar]
  33. Lee Y.T. Tan Y.J. Oon C.E. Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine. Acta Pharm. Sin. B 2023 13 2 478 497 10.1016/j.apsb.2022.09.010 36873180
    [Google Scholar]
  34. Song B. Park E.Y. Kim K.J. Ki S.H. Repurposing of benzimidazole anthelmintic drugs as cancer therapeutics. Cancers (Basel) 2022 14 19 4601 10.3390/cancers14194601 36230527
    [Google Scholar]
  35. Nardi M. Cano N.C.H. Simeonov S. Bence R. Kurutos A. Scarpelli R. Wunderlin D. Procopio A. A review on the green synthesis of Benzimidazole derivatives and their pharmacological activities. Catalysts 2023 13 2 392 10.3390/catal13020392
    [Google Scholar]
  36. Hernández-López H. Tejada-Rodríguez C.J. Leyva-Ramos S. A panoramic review of benzimidazole derivatives and their potential biological activity. Mini Rev. Med. Chem. 2022 22 9 1268 1280 10.2174/1389557522666220104150051 34983345
    [Google Scholar]
  37. Rajasekhar S. Maiti B.M. Balamurali M. Chanda K. Synthesis and medicinal applications of benzimidazoles: An overview. Curr. Org. Synth. 2017 14 1 40 60 10.2174/1570179413666160818151932
    [Google Scholar]
  38. Singla P. Luxami V. Paul K. Benzimidazole-biologically attractive scaffold for protein kinase inhibitors. RSC Advances 2014 4 24 12422 12440 10.1039/c3ra46304d
    [Google Scholar]
  39. Ajani O.O. Aderohunmu D.V. Ikpo C.O. Adedapo A.E. Olanrewaju I.O. Functionalized benzimidazole scaffolds: Privileged heterocycle for drug design in therapeutic medicine. Arch. Pharm. (Weinheim) 2016 349 7 475 506 10.1002/ardp.201500464 27213292
    [Google Scholar]
  40. Yadav S Narasimhan B Perspectives of Benzimidazole derivatives as anticancer agents in the new era Anticancer Agents Med Chem 2016 16 11 1403 1425 10.2174/1871520616666151103113412
    [Google Scholar]
  41. Braña M.F. Castellano J.M. Keilhauer G. Machuca A. Martín Y. Redondo C. Schlick E. Walker N. Benzimidazo[1,2-c]quinazolines: A new class of antitumor compounds. Anticancer Drug Des. 1994 9 6 527 538 7880377
    [Google Scholar]
  42. Refaat H.M. Synthesis and anticancer activity of some novel 2-substituted benzimidazole derivatives. Eur. J. Med. Chem. 2010 45 7 2949 2956 10.1016/j.ejmech.2010.03.022 20399544
    [Google Scholar]
  43. Bui H.T.B. Ha Q.T.K. Oh W.K. Vo D.D. Chau Y.N.T. Tu C.T.K. Pham E.C. Tran P.T. Tran L.T. Mai H.V. Microwave assisted synthesis and cytotoxic activity evaluations of new benzimidazole derivatives. Tetrahedron Lett. 2016 57 8 887 891 10.1016/j.tetlet.2016.01.042
    [Google Scholar]
  44. Pham E.C. Le Thi T.V. Ly Hong H.H. Vo Thi B.N. Vong L.B. Vu T.T. Vo D.D. Tran Nguyen N.V. Bao Le K.N. Truong T.N. N, 2,6-Trisubstituted 1 H -benzimidazole derivatives as a new scaffold of antimicrobial and anticancer agents: Design, synthesis, in vitro evaluation, and in silico studies. RSC Advances 2022 13 1 399 420 10.1039/D2RA06667J 36605630
    [Google Scholar]
  45. Pribut N. Basson A.E. van Otterlo W.A.L. Liotta D.C. Pelly S.C. Aryl substituted benzimidazolones as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. ACS Med. Chem. Lett. 2019 10 2 196 202 10.1021/acsmedchemlett.8b00549 30783503
    [Google Scholar]
  46. Achar K.C.S. Hosamani K.M. Seetharamareddy H.R. In-vivo analgesic and anti-inflammatory activities of newly synthesized benzimidazole derivatives. Eur. J. Med. Chem. 2010 45 5 2048 2054 10.1016/j.ejmech.2010.01.029 20133024
    [Google Scholar]
  47. Sharma M.C. Kohli D.V. Sharma S. Benzimidazoles derivatives with (2-6-Chloro-5-nitro-1-[2-(1H-tetrazol-5-yl) biphenyl-4-ylmethyl] 1H-benzoimidazol-2-yl-phenyl)-(substituted-benzylidene)-amine with potential angiotensin II receptor antagonists as antihypertensive activity. Int. J. Drug Deliv. 2010 2 3 228 237 10.5138/ijdd.2010.0975.0215.02033
    [Google Scholar]
  48. Tunçbilek M. Kiper T. Altanlar N. Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA. Eur. J. Med. Chem. 2009 44 3 1024 1033 10.1016/j.ejmech.2008.06.026 18718694
    [Google Scholar]
  49. Zhang H.Z. Damu G.L.V. Cai G.X. Zhou C.H. Design, synthesis and antimicrobial evaluation of novel benzimidazole type of Fluconazole analogues and their synergistic effects with Chloromycin, Norfloxacin and Fluconazole. Eur. J. Med. Chem. 2013 64 329 344 10.1016/j.ejmech.2013.03.049 23644216
    [Google Scholar]
  50. Malasala S. Ahmad M.N. Akunuri R. Shukla M. Kaul G. Dasgupta A. Madhavi Y.V. Chopra S. Nanduri S. Synthesis and evaluation of new quinazoline-benzimidazole hybrids as potent anti-microbial agents against multidrug resistant Staphylococcus aureus and Mycobacterium tuberculosis. Eur. J. Med. Chem. 2021 212 112996 10.1016/j.ejmech.2020.112996 33190958
    [Google Scholar]
  51. Surineni G. Gao Y. Hussain M. Liu Z. Lu Z. Chhotaray C. Islam M.M. Hameed H.M.A. Zhang T. Design, synthesis, and in vitro biological evaluation of novel benzimidazole tethered allylidenehydrazinylmethylthiazole derivatives as potent inhibitors of Mycobacterium tuberculosis. MedChemComm 2019 10 1 49 60 10.1039/C8MD00389K 30774854
    [Google Scholar]
  52. Welage LS Berardi RR Evaluation of omeprazole, lansoprazole, pantoprazole, and rabeprazole in the treatment of acid-related diseases J Am Pharm Assoc (Wash) 2000 40 1 52 62 10.1016/S1086‑5802(16)31036‑1
    [Google Scholar]
  53. Cole D.C. Gross J.L. Comery T.A. Aschmies S. Hirst W.D. Kelley C. Kim J.I. Kubek K. Ning X. Platt B.J. Robichaud A.J. Solvibile W.R. Stock J.R. Tawa G. Williams M.J. Ellingboe J.W. Benzimidazole- and indole-substituted 1,3′-bipyrrolidine benzamides as histamine H3 receptor antagonists. Bioorg. Med. Chem. Lett. 2010 20 3 1237 1240 10.1016/j.bmcl.2009.11.122 20042333
    [Google Scholar]
  54. Mohamed B.G. Abdel-Alim A-A.M. Hussein M.A. Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal, anti-inflammatory and analgesic effects. Acta Pharm. 2006 56 1 31 48 16613733
    [Google Scholar]
  55. Ouattara M. Sissouma D. Koné M.W. Menan H.E. Touré S.A. Ouattara L. Synthesis and anthelmintic activity of some hybrid Benzimidazolyl-chalcone derivatives. Trop. J. Pharm. Res. 2011 10 6 767 775 10.4314/tjpr.v10i6.10
    [Google Scholar]
  56. Bharti N. Shailendra Gonzalez Garza M.T. Cruz-Vega D.E. Castro-Garza J. Saleem K. Naqvi F. Maurya M.R. Azam A. Synthesis, characterization and antiamoebic activity of benzimidazole derivatives and their vanadium and molybdenum complexes. Bioorg. Med. Chem. Lett. 2002 12 6 869 871 10.1016/S0960‑894X(02)00034‑3 11958982
    [Google Scholar]
  57. Valdez-Padilla D. Rodríguez-Morales S. Hernández-Campos A. Hernández-Luis F. Yépez-Mulia L. Tapia-Contreras A. Castillo R. Synthesis and antiprotozoal activity of novel 1-methylbenzimidazole derivatives. Bioorg. Med. Chem. 2009 17 4 1724 1730 10.1016/j.bmc.2008.12.059 19186059
    [Google Scholar]
  58. Bhrigu B. Siddiqui N. Pathak D. Alam M.S. Ali R. Azad B. Anticonvulsant evaluation of some newer benzimidazole derivatives: Design and synthesis. Acta Pol. Pharm. 2012 69 1 53 62 22574507
    [Google Scholar]
  59. Pal R. Kumar B. Akhtar M.J. Chawla P.A. Voltage gated sodium channel inhibitors as anticonvulsant drugs: A systematic review on recent developments and structure activity relationship studies. Bioorg. Chem. 2021 115 105230 10.1016/j.bioorg.2021.105230 34416507
    [Google Scholar]
  60. Pal R. Singh K. Khan S.A. Chawla P. Kumar B. Akhtar M.J. Reactive metabolites of the anticonvulsant drugs and approaches to minimize the adverse drug reaction. Eur. J. Med. Chem. 2021 226 113890 10.1016/j.ejmech.2021.113890 34628237
    [Google Scholar]
  61. Akhtar M.J. Pal R. Singh K. Paul J. Khan S.A. Naim M.J. Overview of chemistry and therapeutic potential of non-nitrogen heterocyclics as anticonvulsant agents. Curr. Neuropharmacol. 2022 20 8 1519 1553 10.2174/1570159X19666210803144815 34344289
    [Google Scholar]
  62. Valdez J. Cedillo R. Hernández-Campos A. Yépez L. Hernández-Luis F. Navarrete-Vázquez G. Tapia A. Cortés R. Hernández M. Castillo R. Synthesis and antiparasitic activity of 1H-benzimidazole derivatives. Bioorg. Med. Chem. Lett. 2002 12 16 2221 2224 10.1016/S0960‑894X(02)00346‑3 12127542
    [Google Scholar]
  63. Pal R. Teli G. Akhtar M.J. Matada G.S.P. The role of natural anti-parasitic guided development of synthetic drugs for leishmaniasis. Eur. J. Med. Chem. 2023 258 115609 10.1016/j.ejmech.2023.115609 37421889
    [Google Scholar]
  64. Ushiroda K. Maruta K. Takazawa T. Nagano T. Taiji M. Kohno T. Sato Y. Horai S. Yanagi K. Nagata R. Synthesis and pharmacological evaluation of novel benzoylazole-based PPAR α/γ activators. Bioorg. Med. Chem. Lett. 2011 21 7 1978 1982 10.1016/j.bmcl.2011.02.032 21377875
    [Google Scholar]
  65. Özil M. Emirik M. Beldüz A. Ülker S. Molecular docking studies and synthesis of novel bisbenzimidazole derivatives as inhibitors of α-glucosidase. Bioorg. Med. Chem. 2016 24 21 5103 5114 10.1016/j.bmc.2016.08.024 27576293
    [Google Scholar]
  66. Alpan A.S. Sarıkaya G. Çoban G. Parlar S. Armagan G. Alptüzün V. Mannich‐Benzimidazole Derivatives as Antioxidant and Anticholinesterase Inhibitors: Synthesis, Biological Evaluations, and Molecular Docking Study. Arch. Pharm. (Weinheim) 2017 350 7 e1600351 10.1002/ardp.201600351 28379621
    [Google Scholar]
  67. Karmaker N. Lira D.N. Das B.K. Kumar U. Rouf A.S.S. Synthesis and antioxidant activity of some novel benzimidazole derivatives. DUJPS 2018 16 2 245 249 10.3329/dujps.v16i2.35263
    [Google Scholar]
  68. Rashid M. Husain A. Mishra R. Synthesis of benzimidazoles bearing oxadiazole nucleus as anticancer agents. Eur. J. Med. Chem. 2012 54 855 866 10.1016/j.ejmech.2012.04.027 22608854
    [Google Scholar]
  69. Sarhan A.A.O. Al-Dhfyan A. Al-Mozaini M.A. Adra C.N. Aboul-Fadl T. Cell cycle disruption and apoptotic activity of 3-aminothiazolo[3,2-a]benzimidazole-2-carbonitrile and its homologues. Eur. J. Med. Chem. 2010 45 6 2689 2694 10.1016/j.ejmech.2010.02.025 20226574
    [Google Scholar]
  70. Guan Q. Han C. Zuo D. Zhai M. Li Z. Zhang Q. Zhai Y. Jiang X. Bao K. Wu Y. Zhang W. Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities. Eur. J. Med. Chem. 2014 87 306 315 10.1016/j.ejmech.2014.09.071 25262051
    [Google Scholar]
  71. El Rashedy A.A. Aboul-Enein H.Y. Benzimidazole derivatives as potential anticancer agents. Mini Rev. Med. Chem. 2013 13 3 399 407 23190032
    [Google Scholar]
  72. Kanwal A. Saddique F.A. Aslam S. Ahmad M. Zahoor A.F. Mohsin N-A. Mohsin N-u-A. Benzimidazole ring system as a privileged template for anticancer agents. Pharm. Chem. J. 2018 51 12 1068 1077 10.1007/s11094‑018‑1742‑4
    [Google Scholar]
  73. Cheong J.E. Zaffagni M. Chung I. Xu Y. Wang Y. Jernigan F.E. Zetter B.R. Sun L. Synthesis and anticancer activity of novel water soluble benzimidazole carbamates. Eur. J. Med. Chem. 2018 144 372 385 10.1016/j.ejmech.2017.11.037 29288939
    [Google Scholar]
  74. Akhtar M.J. Siddiqui A.A. Khan A.A. Ali Z. Dewangan R.P. Pasha S. Yar M.S. Design, synthesis, docking and QSAR study of substituted benzimidazole linked oxadiazole as cytotoxic agents, EGFR and erbB2 receptor inhibitors. Eur. J. Med. Chem. 2017 126 853 869 10.1016/j.ejmech.2016.12.014 27987485
    [Google Scholar]
  75. Akkoç S. Kayser V. İlhan İ.Ö. Hibbs D.E. Gök Y. Williams P.A. Hawkins B. Lai F. New compounds based on a benzimidazole nucleus: Synthesis, characterization and cytotoxic activity against breast and colon cancer cell lines. J. Organomet. Chem. 2017 839 98 107 10.1016/j.jorganchem.2017.03.037
    [Google Scholar]
  76. Bielawski K. Wołczyński S. Bielawska A. Inhibition of DNA topoisomerase I and II, and growth inhibition of MDA-MB-231 human breast cancer cells by bis-benzimidazole derivatives with alkylating moiety. Pol. J. Pharmacol. 2004 56 3 373 378 15215569
    [Google Scholar]
  77. Li P. Zhang W. Jiang H. Li Y. Dong C. Chen H. Zhang K. Du Z. Design, synthesis and biological evaluation of benzimidazole–rhodanine conjugates as potent topoisomerase II inhibitors. MedChemComm 2018 9 7 1194 1205 10.1039/C8MD00278A 30109008
    [Google Scholar]
  78. Molehin D. Rasha F. Rahman R.L. Pruitt K. Regulation of aromatase in cancer. Mol. Cell. Biochem. 2021 476 6 2449 2464 10.1007/s11010‑021‑04099‑0 33599895
    [Google Scholar]
  79. Sağlık B.N. Şen A.M. Evren A.E. Çevik U.A. Osmaniye D. Kaya Çavuşoğlu B. Levent S. Karaduman A.B. Özkay Y. Kaplancıklı Z.A. Synthesis, investigation of biological effects and in silico studies of new benzimidazole derivatives as aromatase inhibitors. Z. Naturforsch. C J. Biosci. 2020 75 9-10 353 362 10.1515/znc‑2020‑0104 32681791
    [Google Scholar]
  80. Palma J.P. Wang Y.C. Rodriguez L.E. Montgomery D. Ellis P.A. Bukofzer G. Niquette A. Liu X. Shi Y. Lasko L. Zhu G.D. Penning T.D. Giranda V.L. Rosenberg S.H. Frost D.J. Donawho C.K. ABT-888 confers broad in vivo activity in combination with temozolomide in diverse tumors. Clin. Cancer Res. 2009 15 23 7277 7290 10.1158/1078‑0432.CCR‑09‑1245 19934293
    [Google Scholar]
  81. Wagner L. Profile of veliparib and its potential in the treatment of solid tumors. OncoTargets Ther. 2015 8 1931 1939 10.2147/OTT.S69935 26251615
    [Google Scholar]
  82. Raheem F. Ofori H. Simpson L. Shah V. Abemaciclib: the first FDA-approved CDK4/6 inhibitor for the adjuvant treatment of HR+ HER2− early breast cancer. Ann. Pharmacother. 2022 56 11 1258 1266 10.1177/10600280211073322 35135362
    [Google Scholar]
  83. Zhang Q.W. Ye Z.D. Shen C. Tie H.X. Wang L. Shi L. Synthesis of novel 6,7-dimethoxy-4-anilinoquinolines as potent c-Met inhibitors. J. Enzyme Inhib. Med. Chem. 2019 34 1 124 133 10.1080/14756366.2018.1533822 30422010
    [Google Scholar]
  84. Ricciardelli C. Bianco-Miotto T. Jindal S. Butler L.M. Leung S. McNeil C.M. O’Toole S.A. Ebrahimie E. Millar E.K.A. Sakko A.J. Ruiz A.I. Vowler S.L. Huntsman D.G. Birrell S.N. Sutherland R.L. Palmieri C. Hickey T.E. Tilley W.D. The magnitude of androgen receptor positivity in breast cancer is critical for reliable prediction of disease outcome. Clin. Cancer Res. 2018 24 10 2328 2341 10.1158/1078‑0432.CCR‑17‑1199 29514843
    [Google Scholar]
  85. Yamori T. Matsunaga A. Sato S. Yamazaki K. Komi A. Ishizu K. Mita I. Edatsugi H. Matsuba Y. Takezawa K. Nakanishi O. Kohno H. Nakajima Y. Komatsu H. Andoh T. Tsuruo T. Potent antitumor activity of MS-247, a novel DNA minor groove binder, evaluated by an in vitro and in vivo human cancer cell line panel. Cancer Res. 1999 59 16 4042 4049 10463605
    [Google Scholar]
  86. Rashid M. Husain A. Mishra R. Karim S. Khan S. Ahmad M. Al-wabel N. Husain A. Ahmad A. Khan S.A. Design and synthesis of benzimidazoles containing substituted oxadiazole, thiadiazole and triazolo-thiadiazines as a source of new anticancer agents. Arab. J. Chem. 2019 12 8 3202 3224 10.1016/j.arabjc.2015.08.019
    [Google Scholar]
  87. Kamal A. Praveen Kumar P. Sreekanth K. Seshadri B.N. Ramulu P. Synthesis of new benzimidazole linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates with efficient DNA-binding affinity and potent cytotoxicity. Bioorg. Med. Chem. Lett. 2008 18 8 2594 2598 10.1016/j.bmcl.2008.03.039 18378445
    [Google Scholar]
  88. Karthikeyan C. Solomon V.R. Lee H. Trivedi P. Synthesis and biological evaluation of 2-(phenyl)-3H-benzo[d]imidazole-5-carboxylic acids and its methyl esters as potent anti-breast cancer agents. Arab. J. Chem. 2017 10 S1788 S1794 10.1016/j.arabjc.2013.07.003
    [Google Scholar]
  89. Hasanpourghadi M. Pandurangan A.K. Karthikeyan C. Trivedi P. Mustafa M.R. Mechanisms of the anti-tumor activity of Methyl 2-(-5-fluoro-2-hydroxyphenyl)-1 H-benzo[d]imidazole-5-carboxylate against breast cancer in vitro and in vivo. Oncotarget 2017 8 17 28840 28853 10.18632/oncotarget.16263 28392503
    [Google Scholar]
  90. Blajeski A.L. Phan V.A. Kottke T.J. Kaufmann S.H. G1 and G2 cell-cycle arrest following microtubule depolymerization in human breast cancer cells. J. Clin. Invest. 2002 110 1 91 99 10.1172/JCI13275 12093892
    [Google Scholar]
  91. Singla P. Luxami V. Paul K. Triazine–benzimidazole hybrids: Anticancer activity, DNA interaction and dihydrofolate reductase inhibitors. Bioorg. Med. Chem. 2015 23 8 1691 1700 10.1016/j.bmc.2015.03.012 25792141
    [Google Scholar]
  92. Raimondi M.V. Randazzo O. La Franca M. Barone G. Vignoni E. Rossi D. Collina S. DHFR inhibitors: Reading the past for discovering novel anticancer agents. Molecules 2019 24 6 1140 10.3390/molecules24061140 30909399
    [Google Scholar]
  93. Hontecillas-Prieto L. Flores-Campos R. Silver A. de Álava E. Hajji N. García-Domínguez D.J. Synergistic enhancement of cancer therapy using HDAC inhibitors: Opportunity for clinical trials. Front. Genet. 2020 11 578011 10.3389/fgene.2020.578011 33024443
    [Google Scholar]
  94. Lee D.H. Kim G.W. Jeon Y.H. Yoo J. Lee S.W. Kwon S.H. Advances in histone demethylase KDM4 as cancer therapeutic targets. FASEB J. 2020 34 3 3461 3484 10.1096/fj.201902584R 31961018
    [Google Scholar]
  95. Kuo K.T. Huang W.C. Bamodu O.A. Lee W.H. Wang C.H. Hsiao M. Wang L.S. Yeh C.T. Histone demethylase JARID1B/KDM5B promotes aggressiveness of non-small cell lung cancer and serves as a good prognostic predictor. Clin. Epigenetics 2018 10 1 107 10.1186/s13148‑018‑0533‑9 30092824
    [Google Scholar]
  96. Alhazzazi T.Y. Kamarajan P. Verdin E. Kapila Y.L. SIRT3 and cancer: Tumor promoter or suppressor? Biochimica et Biophysica Acta (BBA)-. Rev. Can. 2011 1816 1 80 88
    [Google Scholar]
  97. Saunders L.R. Verdin E. Sirtuins: Critical regulators at the crossroads between cancer and aging. Oncogene 2007 26 37 5489 5504 10.1038/sj.onc.1210616 17694089
    [Google Scholar]
  98. Neoadjuvant Chemotherapy Docetaxel With or Without SELUMETINIB in Patients With Triple Negative Breast Cancer https://clinicaltrials.gov/study/NCT02685657?cond=Breast%20cancer&term=Selumetinib&rank=8
    [Google Scholar]
  99. Beach D.H. Goad L.J. Berman J.D. Ellenberger T.E. Beverley S.M. Holz G.G. Effects of a squalene-2, 3-epoxidase inhibitor on propagation and sterol biosynthesis of Leishmania promastigotes and amastigotes. Leishmaniasis. 1989 885 890
    [Google Scholar]
  100. Diaz-Gonzalez R. Kuhlmann F.M. Galan-Rodriguez C. da Silva L.M. Saldivia M. Karver C.E. Rodriguez A. Beverley S.M. Navarro M. Pollastri M.P. The susceptibility of trypanosomatid pathogens to PI3/mTOR kinase inhibitors affords a new opportunity for drug repurposing. PLoS Negl. Trop. Dis. 2011 5 8 e1297 10.1371/journal.pntd.0001297 21886855
    [Google Scholar]
  101. Akhoundi M. Kuhls K. Cannet A. Votýpka J. Marty P. Delaunay P. Sereno D. A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies. PLoS Negl. Trop. Dis. 2016 10 3 e0004349 10.1371/journal.pntd.0004349 26937644
    [Google Scholar]
  102. Souza T. Trindade D. Tonoli C. Santos C. Molecular adaptability of nucleoside diphosphate kinase b from trypanosomatid parasites: Stability, oligomerization and structural determinants of nucleotide binding. Mol. Biosyst. 2011 7 7 2189 2195 10.1039/c0mb00307g 21528129
    [Google Scholar]
  103. Edwards D.I. Nitroimidazole drugs - action and resistance mechanisms II. Mechanisms of resistance. J. Antimicrob. Chemother. 1993 31 2 201 210 10.1093/jac/31.2.201 8463167
    [Google Scholar]
  104. Bandaru P.K. Satyakameswar Rao N. Radhika G. Venkateswar Rao B. Synthesis of amide derivatives of benzimidazole-isoxazoles as anticancer agents. Chemical Data Collections 2023 44 100994 10.1016/j.cdc.2023.100994
    [Google Scholar]
  105. Nashaat S. Henen M.A. El-Messery S.M. Eisa H. New benzimidazoles targeting breast cancer: Synthesis, Pin1 inhibition, 2D NMR binding, and computational studies. Molecules 2022 27 16 5245 10.3390/molecules27165245 36014485
    [Google Scholar]
  106. Zoatier B. Yildirim M. Alagoz M.A. Yetkin D. Turkmenoglu B. Burmaoglu S. Algul O. N-(benzazol-2-yl)-2-substituted phenylacetamide derivatives: Design, synthesis and biological evaluation against MCF7 breast cancer cell line. J. Mol. Struct. 2023 1285 135513 10.1016/j.molstruc.2023.135513
    [Google Scholar]
  107. Fan C. Zhong T. Yang H. Yang Y. Wang D. Yang X. Xu Y. Fan Y. Design, synthesis, biological evaluation of 6-(2-amino-1H-benzo[d]imidazole-6-yl)quinazolin-4(3H)-one derivatives as novel anticancer agents with Aurora kinase inhibition. Eur. J. Med. Chem. 2020 190 112108 10.1016/j.ejmech.2020.112108 32058239
    [Google Scholar]
  108. Çevik U.A. Celik I. Mella J. Mellado M. Özkay Y. Kaplancıklı Z.A. Design, synthesis, and molecular modeling studies of a novel benzimidazole as an aromatase inhibitor. ACS Omega 2022 7 18 16152 16163 10.1021/acsomega.2c01497 35571854
    [Google Scholar]
  109. Quy N.P. Hue B.T.B. Do K.M. Quy H.T.K. De T.Q. Phuong T.T.B. Trang P.C. Quoc N.C. Morita H. Design, synthesis and cytotoxicity Evalufation of substituted Benzimidazole conjugated 1,3,4-Oxadiazoles. Chem. Pharm. Bull. (Tokyo) 2022 70 6 448 453 10.1248/cpb.c22‑00162 35650042
    [Google Scholar]
  110. Nazreen S. Almalki A.S.A. Elbehairi S.E.I. Shati A.A. Alfaifi M.Y. Elhenawy A.A. Alsenani N.I. Alfarsi A. Alhadhrami A. Alqurashi E.A. Alam M.M. Cell cycle arrest and apoptosis-inducing ability of benzimidazole derivatives: Design, synthesis, docking, and biological evaluation. Molecules 2022 27 20 6899 10.3390/molecules27206899 36296495
    [Google Scholar]
  111. 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]
  112. Karadayi F.Z. Yaman M. Kisla M.M. Konu O. Ates-Alagoz Z. Design, synthesis, anticancer activity, molecular docking and ADME studies of novel methylsulfonyl indole-benzimidazoles in comparison with ethylsulfonyl counterparts. New J. Chem. 2021 45 20 9010 9019 10.1039/D1NJ01019K
    [Google Scholar]
  113. 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]
  114. Siddig L.A. Khasawneh M.A. Samadi A. Saadeh H. Abutaha N. Wadaan M.A. Synthesis of novel thiourea-/urea-benzimidazole derivatives as anticancer agents. Open Chem. 2021 19 1 1062 1073 10.1515/chem‑2021‑0093
    [Google Scholar]
  115. Nashaat S. Henen M.A. El-Messery S.M. Eisa H. Synthesis, state-of-the-art NMR-binding and molecular modeling study of new benzimidazole core derivatives as Pin1 inhibitors: Targeting breast cancer. Bioorg. Med. Chem. 2020 28 11 115495 10.1016/j.bmc.2020.115495 32307260
    [Google Scholar]
  116. Othman D.I.A. Hamdi A. Tawfik S.S. Elgazar A.A. Mostafa A.S. Identification of new benzimidazole-triazole hybrids as anticancer agents: multi-target recognition, in vitro and in silico studies. J. Enzyme Inhib. Med. Chem. 2023 38 1 2166037 10.1080/14756366.2023.2166037 36651111
    [Google Scholar]
  117. Alzahrani H.A. Alam M.M. Elhenawy A.A. Malebari A.M. Nazreen S. Synthesis, antiproliferative, docking and DFT studies of benzimidazole derivatives as EGFR inhibitors. J. Mol. Struct. 2022 1253 132265 10.1016/j.molstruc.2021.132265
    [Google Scholar]
  118. Gaikwad N.B. Bansode S. Biradar S. Ban M. Srinivas N. Godugu C. Yaddanapudi V.M. New 3‐(1 H ‐benzo[ d ]imidazol‐2‐yl)quinolin‐2(1 H )‐one‐based triazole derivatives: Design, synthesis, and biological evaluation as antiproliferative and apoptosis‐inducing agents. Arch. Pharm. (Weinheim) 2021 354 11 2100074 10.1002/ardp.202100074 34346099
    [Google Scholar]
  119. Güner A. Polatli E. Akkan T. Bektaş H. Albay C. Anticancer and antiangiogenesis activities of novel synthesized 2-substitutedbenzimidazoles molecules. Turk. J. Chem. 2019 43 5 1270 1289 10.3906/kim‑1904‑46
    [Google Scholar]
  120. Morcoss MM Abdelhafez ES Abdel-Rahman HM Abdel-Aziz M El-Ella A Dalal A Novel Benzimidazole/Hydrazone derivatives as promising anticancer lead compounds: Design, synthesis, and molecular docking study J Adv Biomed Pharm Sci 2020 3 2 45 52
    [Google Scholar]
  121. Atmaca H. İlhan S. Batır M.B. Pulat Ç.Ç. Güner A. Bektaş H. Novel benzimidazole derivatives: Synthesis, in vitro cytotoxicity, apoptosis and cell cycle studies. Chem. Biol. Interact. 2020 327 109163 10.1016/j.cbi.2020.109163 32534988
    [Google Scholar]
  122. Abbade Y. Kisla M.M. Hassan M.A.K. Celik I. Dogan T.S. Mutlu P. Ates-Alagoz Z. Synthesis, anticancer activity, and in silico modeling of Alkylsulfonyl Benzimidazole derivatives: Unveiling potent Bcl-2 inhibitors for breast cancer. ACS Omega 2024 9 8 9547 9563 10.1021/acsomega.3c09411 38434899
    [Google Scholar]
  123. Wu W. Li S. Chen J. Duo T. Ma C. Design, synthesis and antitumor effects of novel benzimidazole derivatives as PI3K inhibitors. Bioorg. Med. Chem. Lett. 2023 95 129469 10.1016/j.bmcl.2023.129469 37689214
    [Google Scholar]
  124. Abdullah M.N. Abd Hamid S. Muhamad Salhimi S. Jalil N.A.S. Al-Amin M. Jumali N.S. Design and synthesis of 1‑sec/tert‑butyl-2-chloro/nitrophenylbenzimidazole derivatives: Molecular docking and in vitro evaluation against MDA-MB-231 and MCF-7 cell lines. J. Mol. Struct. 2023 1277 134828 10.1016/j.molstruc.2022.134828
    [Google Scholar]
  125. Pham E.C. Thi Le T.V. Truong T.N. Design, synthesis, bio-evaluation, and in silico studies of some N-substituted 6-(chloro/nitro)-1 H -benzimidazole derivatives as antimicrobial and anticancer agents. RSC Advances 2022 12 33 21621 21646 10.1039/D2RA03491C 35975065
    [Google Scholar]
  126. Huynh T.K.C. Nguyen T.H.A. Nguyen T.C.T. Hoang T.K.D. Synthesis and insight into the structure–activity relationships of 2-phenylbenzimidazoles as prospective anticancer agents. RSC Advances 2020 10 35 20543 20551 10.1039/D0RA02282A 35517717
    [Google Scholar]
  127. Zhang Y.L. Yang R. Xia L.Y. Man R.J. Chu Y.C. Jiang A.Q. Wang Z.C. Zhu H.L. Synthesis, anticancer activity and molecular docking studies on 1,2-diarylbenzimidazole analogues as anti-tubulin agents. Bioorg. Chem. 2019 92 103219 10.1016/j.bioorg.2019.103219 31476616
    [Google Scholar]
  128. Mostafa A.S. Gomaa R.M. Elmorsy M.A. Design and synthesis of 2‐phenyl benzimidazole derivatives as VEGFR ‐2 inhibitors with anti‐breast cancer activity. Chem. Biol. Drug Des. 2019 93 4 454 463 10.1111/cbdd.13433 30393973
    [Google Scholar]
  129. Diaconu D. Antoci V. Mangalagiu V. Amariucai-Mantu D. Mangalagiu I.I. Quinoline–imidazole/benzimidazole derivatives as dual-/multi-targeting hybrids inhibitors with anticancer and antimicrobial activity. Sci. Rep. 2022 12 1 16988 10.1038/s41598‑022‑21435‑6 36216981
    [Google Scholar]
  130. Edukondalu P. Sireesha R. Bandaru C.M. Rao M.V.B. Kala P. Raju R.R. 2021
  131. Rasal N.K. Sonawane R.B. Jagtap S.V. Potential 2,4-dimethyl-1H-pyrrole-3-carboxamide bearing benzimidazole template: Design, synthesis, in vitro anticancer and in silico ADME study. Bioorg. Chem. 2020 97 103660 10.1016/j.bioorg.2020.103660 32086056
    [Google Scholar]
  132. Hsieh C.Y. Ko P.W. Chang Y.J. Kapoor M. Liang Y.C. Chu H-L. Lin H-H. Horng J-C. Hsu M-H. Design and synthesis of benzimidazole-chalcone derivatives as potential anticancer agents. Molecules 2019 24 18 3259 10.3390/molecules24183259 31500191
    [Google Scholar]
  133. Padhy G.K. Panda J. Behera A.K. Synthesis and characterization of novel N-Benzylbenzimidazole linked Pyrimidine derivatives as anticancer agents. IJPER 2019 53 2s s129 s134 10.5530/ijper.53.2s.57
    [Google Scholar]
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Benzimidazole Derivatives in Breast Cancer: Target-Specific Therapeutic Breakthroughs
Bentham Science Publishers ; https://doi.org/10.2174/0115680266336395241115092048
/content/journals/ctmc/10.2174/0115680266336395241115092048
/content/journals/ctmc/10.2174/0115680266336395241115092048
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  • Article Type:     Review Article
Keywords: Benzimidazole ; benzimidazole-containing derivatives ; SAR studies ; breast cancer

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