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image of Multimodal Activity of a Novel Compound against Prostate and Pancreatic Cancer

Abstract

Background

Prostate and pancreatic cancers pose significant global health challenges. This study explored the potential of compound 5b, a novel phthalimido-1,3-thiazole derivative, as an anticancer agent against these malignancies.

Methods

, compound 5b exhibited potent cytotoxic activity against both prostate (DU-145 and PC-3) and pancreatic (Panc-1 and Mia Paca-2) cancer cell lines. Notably, it significantly reduced colony formation in PC-3 cells, potentially hindering tumor growth. Furthermore, treatment with compound 5b suppressed cell migration and induced cell cycle arrest in the PC-3 line. Additionally, it triggered cell death through late apoptosis and necrosis at higher concentrations. Safety evaluations in mice revealed no mortality or adverse effects after a 30-day treatment with compound 5b. Key blood parameters (hematology) and biochemical markers of liver and kidney function remained unaltered.

Results

Compound 5b significantly reduced colony formation, suppressed cell migration, and induced cell cycle arrest and apoptosis/necrosis in prostate cancer cells. , safety evaluations showed no adverse effects in treated mice, with blood and biochemical markers remaining normal.

Conclusion

These findings suggest that compound 5b holds promise for further development as a therapeutic option for prostate and pancreatic cancers. Its multimodal activity profile, targeting cell viability, migration, cell cycle progression, and cell death, warrants further investigation.

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2025-03-19
2025-09-13

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References

  1. Matthews H.K. Bertoli C. de Bruin R.A.M. Cell cycle control in cancer. Nat. Rev. Mol. Cell Biol. 2022 23 1 74 88 10.1038/s41580‑021‑00404‑3 34508254
    [Google Scholar]
  2. Chen J. Xia Y. Yao J. Yan K. Zhang J. Lu L. Wang F. Zhou B. Qiu M. Yu Q. Yuan M. Fang W. Tang Y. Xu M. Zhou J. Zhao Y. Wang Q. Ye X. Yin X. Shi Y. Chen X. Zhou J. Yuille A. Liu Z. Zhang L. 2023 10.1109/ICCV51070.2023.01950
  3. Pereira Primo1, W.Q.S. Estimated 2023: Cancer incidence in Brazil. Rev. Bras. Ginecol. Obstet. 2023 45 1 1 2
    [Google Scholar]
  4. Gbolahan O. Hashemi-Sadraei N. Yash S. Williams G. Ramachandran R. Kim Y. Paluri R. Outlaw D. El-Rayes B. Nabell L. Time to treatment initiation and its impact on real‐world survival in metastatic colorectal cancer and pancreatic cancer. Cancer Med. 2023 12 3 3488 3498 10.1002/cam4.5133 35979540
    [Google Scholar]
  5. Wood L.D. Canto M.I. Jaffee E.M. Simeone D.M. Pancreatic cancer: Pathogenesis, screening, diagnosis, and treatment. Gastroenterology 2022 163 2 386 402.e1 10.1053/j.gastro.2022.03.056 35398344
    [Google Scholar]
  6. Ushio J. Kanno A. Ikeda E. Ando K. Nagai H. Miwata T. Kawasaki Y. Tada Y. Yokoyama K. Numao N. Tamada K. Lefor A.K. Yamamoto H. Pancreatic ductal adenocarcinoma: Epidemiology and risk factors. Diagnostics (Basel) 2021 11 3 562 10.3390/diagnostics11030562 33804776
    [Google Scholar]
  7. Siegel R.L. Giaquinto A.N. Jemal A. Cancer statistics, 2024. CA Cancer J. Clin. 2024 74 1 12 49 10.3322/caac.21820 38230766
    [Google Scholar]
  8. Arshad M.F. Alam A. Alshammari A.A. Alhazza M.B. Alzimam I.M. Alam M.A. Mustafa G. Ansari M.S. Alotaibi A.M. Alotaibi A.A. Kumar S. Asdaq S.M.B. Imran M. Deb P.K. Venugopala K.N. Jomah S. Thiazole: A versatile standalone moiety contributing to the development of various drugs and biologically active agents. Molecules 2022 27 13 3994 10.3390/molecules27133994 35807236
    [Google Scholar]
  9. Zahran M.A.H. Abdin Y.G. Osman A.M.A. Gamal-Eldeen A.M. Talaat R.M. Pedersen E.B. Synthesis and evaluation of thalidomide and phthalimide esters as antitumor agents. Arch. Pharm. (Weinheim) 2014 347 9 642 649 10.1002/ardp.201400073 24943104
    [Google Scholar]
  10. Hawtin R.E. Stockett D.E. Byl J.A.W. McDowell R.S. Tan N. Arkin M.R. Conroy A. Yang W. Osheroff N. Fox J.A. Voreloxin is an anticancer quinolone derivative that intercalates DNA and poisons topoisomerase II. PLoS One 2010 5 4 e10186 10.1371/journal.pone.0010186 20419121
    [Google Scholar]
  11. Oliveira A.R. dos Santos F.A. Ferreira L.P.L. Pitta M.G.R. Silva M.V.O. Cardoso M.V.O. Pinto A.F. Marchand P. de Melo Rêgo M.J.B. Leite A.C.L. Synthesis, anticancer activity and mechanism of action of new phthalimido-1,3-thiazole derivatives. Chem. Biol. Interact. 2021 347 109597 10.1016/j.cbi.2021.109597 34303695
    [Google Scholar]
  12. Annexes CONCEA normative resolution: Studies domestics animals. 2019.
  13. Strategies - 2019 - National strategy for science, technology and innovation. 2019 https://mohesr.gov.eg/en-us/Documents/sr_strategy.pdf
  14. Lopez J.S. Banerji U. Combine and conquer: Challenges for targeted therapy combinations in early phase trials. Nat. Rev. Clin. Oncol. 2017 14 1 57 66 10.1038/nrclinonc.2016.96 27377132
    [Google Scholar]
  15. Kopetz S. Grothey A. Yaeger R. Van Cutsem E. Desai J. Yoshino T. Wasan H. Ciardiello F. Loupakis F. Hong Y.S. Steeghs N. Guren T.K. Arkenau H.T. Garcia-Alfonso P. Pfeiffer P. Orlov S. Lonardi S. Elez E. Kim T.W. Schellens J.H.M. Guo C. Krishnan A. Dekervel J. Morris V. Calvo Ferrandiz A. Tarpgaard L.S. Braun M. Gollerkeri A. Keir C. Maharry K. Pickard M. Christy-Bittel J. Anderson L. Sandor V. Tabernero J. Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer. N. Engl. J. Med. 2019 381 17 1632 1643 10.1056/NEJMoa1908075 31566309
    [Google Scholar]
  16. Jaaks P. Coker E.A. Vis D.J. Edwards O. Carpenter E.F. Leto S.M. Dwane L. Sassi F. Lightfoot H. Barthorpe S. van der Meer D. Yang W. Beck A. Mironenko T. Hall C. Hall J. Mali I. Richardson L. Tolley C. Morris J. Thomas F. Lleshi E. Aben N. Benes C.H. Bertotti A. Trusolino L. Wessels L. Garnett M.J. Effective drug combinations in breast, colon and pancreatic cancer cells. Nature 2022 603 7899 166 173 10.1038/s41586‑022‑04437‑2 35197630
    [Google Scholar]
  17. Zimmermann M.O. Lange A. Wilcken R. Cieslik M.B. Exner T.E. Joerger A.C. Koch P. Boeckler F.M. Halogen-enriched fragment libraries as chemical probes for harnessing halogen bonding in fragment-based lead discovery. Future Med. Chem. 2014 6 6 617 639 10.4155/fmc.14.20 24895892
    [Google Scholar]
  18. Dammann M. Stahlecker J. Zimmermann M.O. Klett T. Rotzinger K. Kramer M. Coles M. Stehle T. Boeckler F.M. Screening of a halogen-enriched fragment library leads to unconventional binding modes. J. Med. Chem. 2022 65 21 14539 14552 10.1021/acs.jmedchem.2c00951 36288453
    [Google Scholar]
  19. Thapa Magar T.B. Kadayat T.M. Lee H.J. Park S. Bist G. Shrestha A. Kwon Y. Lee E.S. 2-Chlorophenyl-substituted benzofuro[3,2-b]pyridines with enhanced topoisomerase inhibitory activity: The role of the chlorine substituent. Bioorg. Med. Chem. Lett. 2017 27 15 3279 3283 10.1016/j.bmcl.2017.06.025 28633898
    [Google Scholar]
  20. O’Bryan J.P. Pharmacological targeting of RAS: Recent success with direct inhibitors. Pharmacol. Res. 2019 139 503 511 10.1016/j.phrs.2018.10.021 30366101
    [Google Scholar]
  21. Belluti S. Orteca G. Semeghini V. Rigillo G. Parenti F. Ferrari E. Imbriano C. Potent anti-cancer properties of phthalimide-based curcumin derivatives on prostate tumor cells. Int. J. Mol. Sci. 2018 20 1 28 10.3390/ijms20010028 30577600
    [Google Scholar]
  22. Zheng S. Zhong Q. Jiang Q. Mottamal M. Zhang Q. Zhu N. Burow M.E. Worthylake R.A. Wang G. Discovery of a series of thiazole derivatives as novel inhibitors of metastatic cancer cell migration and invasion. ACS Med. Chem. Lett. 2013 4 2 191 196 10.1021/ml300322n 23526571
    [Google Scholar]
  23. Aktas A. Barut Celepci D. Gok Y. Taslimi P. Akincioglu H. Gulcin İ. A novel Ag-N-heterocyclic carbene complex bearing the hydroxyethyl ligand: Synthesis, characterization, crystal and spectral structures and bioactivity properties. Crystals (Basel) 2020 10 3 171 10.3390/cryst10030171
    [Google Scholar]
  24. Tantak P. A facile and microwave-assisted rapid synthesis of 2-arylamino-4-(3′-Indolyl)-thiazoles as apoptosis inducing cytotoxic agents. Anticancer. Agents Med. Chem. 2017 17 442 455
    [Google Scholar]
  25. Nagireddy P.K.R. Kommalapati V.K. Siva Krishna V. Sriram D. Tangutur A.D. Kantevari S. Imidazo[2,1-b]thiazole-Coupled natural noscapine derivatives as anticancer agents. ACS Omega 2019 4 21 19382 19398 10.1021/acsomega.9b02789 31763563
    [Google Scholar]
  26. Conroy T. Desseigne F. Ychou M. Bouché O. Guimbaud R. Bécouarn Y. Adenis A. Raoul J.L. Gourgou-Bourgade S. de la Fouchardière C. Bennouna J. Bachet J.B. Khemissa-Akouz F. Péré-Vergé D. Delbaldo C. Assenat E. Chauffert B. Michel P. Montoto-Grillot C. Ducreux M. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N. Engl. J. Med. 2011 364 19 1817 1825 10.1056/NEJMoa1011923 21561347
    [Google Scholar]
  27. Saung M.T. Zheng L. Current standards of chemotherapy for pancreatic cancer. Clin. Ther. 2017 39 11 2125 2134 10.1016/j.clinthera.2017.08.015 28939405
    [Google Scholar]
  28. Schlick K. Magnes T. Ratzinger L. Jaud B. Weiss L. Melchardt T. Greil R. Egle A. Novel models for prediction of benefit and toxicity with FOLFIRINOX treatment of pancreatic cancer using clinically available parameters. PLoS One 2018 13 11 e0206688 10.1371/journal.pone.0206688 30412592
    [Google Scholar]
  29. van Eijck C.W.F. Sabroso-Lasa S. Strijk G.J. Mustafa D.A.M. Fellah A. Koerkamp B.G. Malats N. van Eijck C.H.J. A liquid biomarker signature of inflammatory proteins accurately predicts early pancreatic cancer progression during FOLFIRINOX chemotherapy. Neoplasia 2024 49 100975 10.1016/j.neo.2024.100975 38335839
    [Google Scholar]
  30. McGill M.R. The past and present of serum aminotransferases and the future of liver injury biomarkers. EXCLI J. 2016 15 817 828 28337112
    [Google Scholar]
  31. Amin S. Sheikh K.A. Iqubal A. Ahmed Khan M. Shaquiquzzaman M. Tasneem S. Khanna S. Najmi A.K. Akhter M. Haque A. Anwer T. Mumtaz Alam M. Synthesis, in-Silico studies and biological evaluation of pyrimidine based thiazolidinedione derivatives as potential anti-diabetic agent. Bioorg. Chem. 2023 134 106449 10.1016/j.bioorg.2023.106449 36889200
    [Google Scholar]
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Multimodal Activity of a Novel Compound against Prostate and Pancreatic Cancer
Bentham Science Publishers ; https://doi.org/10.2174/0115680266351687250309020134
/content/journals/ctmc/10.2174/0115680266351687250309020134
/content/journals/ctmc/10.2174/0115680266351687250309020134
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  • Article Type:     Research Article
Keywords: Anti-tumor activity ; chemotherapy ; cancer

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