Novel 3-Substituted 8-Methoxycoumarin Derivatives as Anti-Breast Cancer Drugs
Source abstract
Abstract
Scientists have been interested in hybrid coumarin derivatives due to their wide clinical anticancer use. Herein, ethyl 8-methoxycoumarin-3-carboxylate (Compound 1) served as the starting material for the synthesis of a series of novel hybrid coumarin derivatives (Compounds 3–6). Their structure was determined using 13C NMR, 1H NMR, elemental analysis, and mass spectrometry. The in vitro cytotoxic activities of coumarin derivatives (Compounds 3, 5, and 6) and brominated coumarin derivatives (Compounds 4, 8, and 9) against MCF-7 and MDA-MB-231 were evaluated. Several substances have been identified as promising candidates for future study, especially Compound 6 due to its potent activity against β-tubulin (TUB) polymerization, sulfatase, and aromatase enzymes. It also has a role in inducing cell-cycle arrest at the S phase in the MCF-7 cell line, as well as apoptosis.
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Research context
OpenAlex topics: Synthesis and biological activity · Synthesis of Organic Compounds · Plant chemical constituents analysis
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
Affiliations
Department of Chemistry, College of Science, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia
Department of Chemistry, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Department of Biochemistry, College of Science, University of Jeddah, P.O. Box 34, Jeddah 23445, Saudi Arabia
Department of Biochemistry, Faculty of Science, Port-Said University, Port-Said 42526, Egypt
Department of Biochemistry, Faculty of Pharmacy, Port-Said University, Port-Said 42526, Egypt
Anatomy Department, College of Medicine, King Khalid University, P.O. Box 62529, Abha 61413, Saudi Arabia
Department of Biotechnology, College of Sciences, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Department of Chemistry, Faculty of Science, Port-Said University, Port-Said 42526, Egypt
Funding
Deanship of Scientific Research at King Khalid University · Princess Nourah bint Abdulrahman University
References (54)
Show source-provided references
1. Design Strategies, Structure Activity Relationship and Mechanistic Insights for Purine as Kinase Inhibitors10.1016/j.ejmech.2016.02.018 ↗
2. Rational Approaches, Design Strategies, Structure Activity Relationship and Mechanistic Insights for Anticancer Hybrids10.1016/j.ejmech.2014.03.018 ↗
3. Tubulin Inhibitors: A Patent Survey10.2174/1574892809666140520150459 ↗
4. The Medicinal Chemistry of Hybrid-based Drugs Targeting Multiple Sites of Action10.2174/156802611798184382 ↗
5. Multifunctional compounds: Smart molecules for multifactorial diseases10.1016/j.ejmech.2014.01.060 ↗
6. The emergence of designed multiple ligands for neurodegenerative disorders10.1016/j.pneurobio.2011.04.010 ↗
7. One-compound-multiple-targets strategy to combat Alzheimer’s disease10.1016/j.febslet.2005.09.006 ↗
8. Multimodal drugs and their future for Alzheimer’s and Parkinson’s disease10.1016/B978-0-12-386467-3.00006-6 ↗
9. Flores-Morales, V., Villasana-Ruíz, A.P., Garza-Veloz, I., González-Delgado, S., and Martinez-Fierro, M.L. (2023). Therapeutic Effects of Coumarins with Different Substitution Patterns. Molecules, 28.10.3390/molecules28052413 ↗
10. Design, synthesis, and vasorelaxant and platelet antiaggregatory activities of coumarin–resveratrol hybrids. Bioorg10.1016/j.bmcl.2005.10.013 ↗
11. Practical synthesis of maleimides and coumarin-linked probes for protein and antibodylabellingviareduction of native disulfides10.1039/b904060a ↗
12. Synthesis and evaluation of the antioxidant and anti-inflammatory activity of novel coumarin-3-aminoamides and their alpha-lipoic acid adducts10.1016/j.ejmech.2008.12.027 ↗
13. Indole-coumarin-thiadiazole hybrid: An appraisal of their MCF-7 cell growth inhibition, apoptic, antimetastatic and computational BCL-2 binding potential10.1016/j.ejmech.2017.05.032 ↗
14. Design, synthesis and anticancer screening of 3-(3-(substitutedphenyl)acryloyl)-2H-chromen-2-ones as selective anti-brast cancer agent10.1016/j.biopha.2017.02.089 ↗
15. Synthesis and biological evaluation of naphthoquinpne-coumarin conjugates as topoisomerase II inhibitors10.1016/j.bmcl.2016.12.040 ↗
16. Design and synthesis of new coumarin hybrids and insight into their mode of antiproliferative action10.1016/j.bmc.2016.12.019 ↗
17. Global Cancer Statistics10.3322/caac.20107 ↗
18. Kim, S.-K. (2015). Handbook of Anticancer Drugs from Marine Origin, Springer International Publishing.10.1007/978-3-319-07145-9 ↗
19. WHO (2013). Cancer Fact Sheet No. 297, World Health Organization.
20. Design, Synthesis, and Anti-Breast Cancer Activity of Some Hybrid Molecules Containing Coumarin Moiety10.1134/S1068162021010180 ↗
21. Synthesis and Biological Evaluation of Some New 3,4-Disubstituted Coumarin Derivatives as Anticancer Agents
22. Synthesis and Antiproliferative Activity of Some New Coumarin Derivatives Derived from 8-Hydroxycoumarin10.1134/S106816202102028X ↗
23. Salem, M.G., Abu-El Maaty, D.M., El-Deen, Y.I.M., Elesawy, B.H., El Askary, A., Saleh, A., Saied, E.M., and El Behery, M. (2022). Novel 1,3-Thiazole Analogues with Potent Activity against Breast Cancer: A Design, Synthesis, In Vitro, and In Silico Study. Molecules, 27.10.3390/molecules27154898 ↗
24. Development of [1,2]oxazoloisoindoles tubulin polymerization inhibitors: Further chemical modifications and potential therapeutic effects against lymphomas10.1016/j.ejmech.2022.114744 ↗
25. Simple monocyclic pyrimidine analogs as microtubule targeting agents binding to the colchicine site10.1016/j.bmc.2023.117217 ↗
26. Recurrence of the oxazole motif in tubulin colchicine site inhibitors with anti-tumor activity
27. Chen, Z.-H., Xu, R.-M., Zheng, G.-H., Jin, Y.-Z., Li, Y., Chen, X.-Y., and Tian, Y.-S. (2023). Development of Combretastatin A-4 Analogues as Potential Anticancer Agents with Improved Aqueous Solubility. Molecules, 28.10.3390/molecules28041717 ↗
28. Comprehensive review on current developments of quinoline-based anticancer agents10.1016/j.arabjc.2016.10.009 ↗
29. Sulfatases: Critical Enzymes for Algal Polysaccharide Processing10.3389/fpls.2022.837636 ↗
30. Sculpting tissues by phase transitions10.1038/s41467-022-28151-9 ↗
31. Design, synthesis and biological evaluation of combretastatin A-4 sulfamate derivatives as potential anti-cancer agents10.1039/D0MD00372G ↗
32. Phosphate tricyclic coumarin analogs as steroid sulfatase inhibitors: Synthesis and biological activity10.1039/C4RA07135B ↗
33. Aromatase inhibitors in breast cancer therapy. Expert10.1586/14737140.2.2.181 ↗
34. Molecular pharmacology of aromatase and its regulation by endogenous and exogenous agents10.1016/S0960-0760(01)00127-3 ↗
35. Aromatase inhibitors in the treatment of advanced breast cancer10.1016/0305-7372(89)90012-1 ↗
36. Recent developments in aromatase inhibition as a potential treatment for oestrogen-dependent breast cancer10.1016/S0079-6468(08)70242-X ↗
37. Selective estrogen receptor modulators (SERMs) and their roles in breast cancer prevention10.1016/S1471-4914(02)02282-7 ↗
38. Biological rationale for endocrine therapy in breast cancer10.1016/S1521-690X(03)00044-7 ↗
39. Inhibition of estrone sulfatase (ES) by derivatives of 4-[(aminosulfonyl)oxy] benzoic acid10.1016/S0960-894X(02)00383-9 ↗
40. Medicinal chemistry aspects and synthetic strategies of coumarin as aromatase inhibitors: An overview10.1007/s12032-022-01916-4 ↗
41. Coleman, W.B., and Tsongalis, E. (2020). Chapter 26-Molecular Biology of Breast Cancer, Academic Press. [2nd ed.].
42. The Role of Progesterone Receptors in Breast Cancer10.2147/DDDT.S336643 ↗
43. Influence of CYP19A1 gene expression levels in women with breast cancer: A systematic review of the literature10.6061/clinics/2021/e2846 ↗
44. Testa, U., Castelli, G., and Pelosi, E. (2020). Breast Cancer: A Molecularly Heterogenous Disease Needing Subtype-Specific Treatments. Med. Sci., 8.10.3390/medsci8010018 ↗
45. Role of cytochrome P450 genes in breast cancer etiology and treatment: Effects on estrogen biosynthesis, metabolism, and response to endocrine therapy10.1007/s10552-014-0519-7 ↗
46. Genetic Polymorphisms of the CYP19A1 Gene and Breast Cancer Survival10.1158/1055-9965.EPI-06-0464 ↗
47. Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells10.1007/s10616-009-9191-2 ↗
48. Design, synthesis and screening of 1, 2, 4-triazinone derivatives as potential antitumor agents with apoptosis inducing activity on MCF-7 breast cancer cell line10.1016/j.ejmech.2018.07.003 ↗
49. Terpinen-4-ol induces apoptosis in human nonsmall cell lung cancer in vitro and in vivo. Evid. Based Complement
50. Synthesis and cytotoxicity screening of some synthesized hybrid nitrogen molecules as anticancer agents10.1016/j.molstruc.2021.130722 ↗
51. 2-Anilinopyrimidine derivatives: Design, synthesis, in vitro anti-proliferative activity, EGFR and ARO inhibitory activity, cell cycle analysis and molecular docking study10.1016/j.bioorg.2020.103798 ↗
52. Structural evidence for ligand specificity in the binding domain of the human androgen receptor: Implications for pathogenic gene mutations10.1074/jbc.M004571200 ↗
53. Testosterone complex and non-steroidal ligands of human aromatase10.1016/j.jsbmb.2018.02.009 ↗
54. MolDock: A new technique for high-accuracy molecular docking10.1021/jm051197e ↗