DNA Base Bioisosteres, Bis-benzoxazoles, Exert Anti-proliferative Effect on Human Prostate and Breast Cancer Cells

Year 2018, Volume: 5 Issue: 3, 1145 - 1152, 01.09.2018

Furkan Ayaz , Rusmeenee Kheeree Qadar Ahmed Isse Ronak Haj Ersan Oztekin Algul

https://doi.org/10.18596/jotcsa.429504

Cited By: 9

Abstract

A series of symmetric bis-benzoxazole
derivatives were synthesized using one-pot cyclisation reaction between 4-chloro
substituted 2-aminophenol and suitable dicarboxylic acids. Synthesized
compounds’ anticancer activities were tested by using MTT assay on human prostate
(DU145) and breast (MCF7) cancer cells. Screening results revealed that all
compounds possessed a high level anti-cancer potential by significantly
decreasing the cell proliferation in prostate and breast cancer cell lines. Our
compounds exerted their anti-proliferative effects in a dose and time dependent
manner. Our results suggest that they can be highly potent since they were biologically
active even at low concentrations. Our study presents a series of new
bis-benzoxazole based compounds with potential therapeutic effects against tumor
cells. Therefore, characterization of new
generation bis-benzoxazole derivatives will have a significant contribution on the
development of new era anti-cancer drug candidates.   

Keywords

Bis-benzoxazole, breast cancer, prostate cancer, anti-proliferative, anti-cancer, MTT

References

• 1. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre M, et al. Global Burden of Disease Cancer Collaboration The Global Burden of Cancer 2013. JAMA Oncol. 2015;2015(1):505–27.
• 2. Biteau B, Hochmuth CE, Jasper H. Maintaining Tissue Homeostasis: Dynamic Control of Somatic Stem Cell Activity. Cell Stem Cell. 2011 Nov;9(5):402–11.
• 3. Alvarado C, Fider NA, Wearing HJ, Komarova NL. Optimizing homeostatic cell renewal in hierarchical tissues. Traulsen A, editor. PLOS Computational Biology. 2018 Feb 15;14(2):e1005967.
• 4. Pellettieri J, Alvarado AS. Cell Turnover and Adult Tissue Homeostasis: From Humans to Planarians. Annual Review of Genetics. 2007 Dec;41(1):83–105.
• 5. Antonello ZA, Reiff T, Dominguez M. Mesenchymal to epithelial transition during tissue homeostasis and regeneration: Patching up the Drosophila midgut epithelium. Fly. 2015 Jul 3;9(3):132–7.
• 6. Hunt T, Nasmyth K, Novak B. The cell cycle. Philosophical Transactions of the Royal Society B: Biological Sciences. 2011 Dec 27;366(1584):3494–7.
• 7. Williams GH, Stoeber K. Cell cycle markers in clinical oncology. Current Opinion in Cell Biology. 2007 Dec;19(6):672–9.
• 8. Bower JJ, Karaca GF, Zhou Y, Simpson DA, Cordeiro-Stone M, Kaufmann WK. Topoisomerase IIα maintains genomic stability through decatenation G2 checkpoint signaling. Oncogene. 2010 Aug;29(34):4787–99.
• 9. Hartwell L, Kastan M. Cell cycle control and cancer. Science. 1994 Dec 16;266(5192):1821–8.
• 10. Classon M, Harlow E. The retinoblastoma tumour suppressor in development and cancer. Nature Reviews Cancer. 2002 Dec;2(12):910–7.
• 11. Xu B, Kim S -t., Kastan MB. Involvement of Brca1 in S-Phase and G2-Phase Checkpoints after Ionizing Irradiation. Molecular and Cellular Biology. 2001 May 15;21(10):3445–50.
• 12. Wang R-H, Yu H, Deng C-X. A requirement for breast-cancer-associated gene 1 (BRCA1) in the spindle checkpoint. Proceedings of the National Academy of Sciences. 2004 Dec 7;101(49):17108–13.
• 13. Santarpia L, Iwamoto T, Di Leo A, Hayashi N, Bottai G, Stampfer M, et al. DNA Repair Gene Patterns as Prognostic and Predictive Factors in Molecular Breast Cancer Subtypes. The Oncologist. 2013 Oct 1;18(10):1063–73.
• 14. Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proceedings of the National Academy of Sciences. 2001 Sep 11;98(19):10869–74.
• 15. Nakagawa T, Hayashita Y, Maeno K, Masuda A, Sugito N, Osada H, et al. Identification of Decatenation G 2 Checkpoint Impairment Independently of DNA Damage G 2 Checkpoint in Human Lung Cancer Cell Lines. Cancer Research. 2004 Jul 15;64(14):4826–32.
• 16. Hinck L, Näthke I. Changes in cell and tissue organization in cancer of the breast and colon. Current Opinion in Cell Biology. 2014 Feb;26:87–95.
• 17. Cho EH, Wendel M, Luttgen M, Yoshioka C, Marrinucci D, Lazar D, et al. Characterization of circulating tumor cell aggregates identified in patients with epithelial tumors. Physical Biology. 2012 Feb 1;9(1):016001.
• 18. De Smedt L, Palmans S, Sagaert X. Tumour budding in colorectal cancer: what do we know and what can we do? Virchows Archiv. 2016 Apr;468(4):397–408.
• 19. Gustavsson B, Carlsson G, Machover D, Petrelli N, Roth A, Schmoll H-J, et al. A Review of the Evolution of Systemic Chemotherapy in the Management of Colorectal Cancer. Clinical Colorectal Cancer. 2015 Mar;14(1):1–10.
• 20. Huang C-Y, Ju D-T, Chang C-F, Muralidhar Reddy P, Velmurugan BK. A review on the effects of current chemotherapy drugs and natural agents in treating non–small cell lung cancer. BioMedicine. 2017 Dec;7(4):23.
• 21. Harrison’s principles of internal medicine [Internet]. NCBI; [cited 2018 Jun 1]. Available from: https://www.ncbi.nlm.nih.gov/nlmcatalog/101643730
• 22. Andreae S, editor. Lexikon der Krankheiten und Untersuchungen. 2., überarbeitete und erw. Aufl. Stuttgart ; New York: G. Thieme; 2008. 1468 p.
• 23. Pearce A, Haas M, Viney R, Pearson S-A, Haywood P, Brown C, et al. Incidence and severity of self-reported chemotherapy side effects in routine care: A prospective cohort study. Ganti AK, editor. PLOS ONE. 2017 Oct 10;12(10):e0184360.
• 24. Ihbe-Heffinger A, Ehlken B, Bernard R, Berger K, Peschel C, Eichler H-G, et al. The impact of delayed chemotherapy-induced nausea and vomiting on patients, health resource utilization and costs in German cancer centers. Annals of Oncology. 2004 Mar;15(3):526–36.
• 25. Khoshbin AR, Mohamadabadi F, Vafaeian F, Babania A, Akbarian S, Khandozi R, et al. The effect of radiotherapy and chemotherapy on osmotic fragility of red blood cells and plasma levels of malondialdehyde in patients with breast cancer. Reports of Practical Oncology & Radiotherapy. 2015 Jul;20(4):305–8.
• 26. Hu Q, Sun W, Wang C, Gu Z. Recent advances of cocktail chemotherapy by combination drug delivery systems. Advanced Drug Delivery Reviews. 2016 Mar;98:19–34.
• 27. Hoelder S, Clarke PA, Workman P. Discovery of small molecule cancer drugs: Successes, challenges and opportunities. Molecular Oncology. 2012 Apr;6(2):155–76.
• 28. Ueki M, Ueno K, Miyadoh S, Abe K, Shibata K, Taniguchi M, et al. UK-1, a novel cytotoxic metabolite from Streptomyces sp. 517-02. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties. The Journal of Antibiotics. 1993;46(7):1089–94.
• 29. Cheng CC, Dong Q, Liu DF, Luo YL, Liu LF, Chen AY, et al. Design of antineoplastic agents on the basis of the 2-phenylnaphthalene-type structural pattern. 2. Synthesis and biological activity studies of benzo[b]naphtho[2,3-d]furan-6,11-dione derivatives. Journal of Medicinal Chemistry. 1993 Dec;36(25):4108–12.
• 30. Kamal A, Srinivasa Reddy T, Polepalli S, Paidakula S, Srinivasulu V, Ganga Reddy V, et al. Synthesis and biological evaluation of 4-aza-2,3-dihydropyridophenanthrolines as tubulin polymerization inhibitors. Bioorganic & Medicinal Chemistry Letters. 2014 Aug;24(15):3356–60.
• 31. Kim JS, Sun Q, Gatto B, Yu C, Liu A, Liu LF, et al. Structure-activity relationships of benzimidazoles and related heterocycles as topoisomerase I poisons. Bioorganic & Medicinal Chemistry. 1996 Apr;4(4):621–30.
• 32. Sun L-Q, Chen J, Bruce M, Deskus JA, Epperson JR, Takaki K, et al. Synthesis and structure–activity relationship of novel benzoxazole derivatives as melatonin receptor agonists. Bioorganic & Medicinal Chemistry Letters. 2004 Jul;14(14):3799–802.
• 33. Ertan T, Yildiz I, Tekiner-Gulbas B, Bolelli K, Temiz-Arpaci O, Ozkan S, et al. Synthesis, biological evaluation and 2D-QSAR analysis of benzoxazoles as antimicrobial agents. European Journal of Medicinal Chemistry. 2009 Feb;44(2):501–10.
• 34. Alper-Hayta S, Arisoy M, Temiz-Arpaci Ö, Yildiz I, Aki E, Özkan S, et al. Synthesis, antimicrobial activity, pharmacophore analysis of some new 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles. European Journal of Medicinal Chemistry. 2008 Nov;43(11):2568–78.
• 35. Sun A, Prussia A, Zhan W, Murray EE, Doyle J, Cheng L-T, et al. Nonpeptide Inhibitors of Measles Virus Entry. Journal of Medicinal Chemistry. 2006 Aug;49(17):5080–92.
• 36. Padmavathi V, Venkatesh BC, Muralikrishna A, Padmaja A. Synthesis and Antioxidant Activity of a New Class of Bis and Tris Heterocycles. Archiv der Pharmazie. 2012 Sep;345(9):745–52.
• 37. Ravez S, Castillo-Aguilera O, Depreux P, Goossens L. Quinazoline derivatives as anticancer drugs: a patent review (2011 – present). Expert Opinion on Therapeutic Patents. 2015 Jul 3;25(7):789–804.