Synthesis And Biological Evaluation of Novel Benzopyran-2-One And 1, 2, 4-Triazole Hybrid Derivatives as Cytotoxic Agents
Keywords:
antiproliferative, apoptosis, benzopyran-2-one, coumarin, drug discovery, triazole, protein tyrosine kinaseAbstract
Triazole's anti-inflammatory properties in cellular assays and benzopyran-2-one's cytotoxic effects against multi-drug resistant cancer cell lines led us to design and synthesize their hybrid compounds and investigate their antiproliferative activity against a panel of five cancer cell lines. Compounds FE-e, FE-f, FE-o and FE-q displayed significant antiproliferative activities against all the cancer cell lines tested, and IC50 values were in the range of 162-164µM/mL against MDA-MB-231, MCF-7, CaCO2, HUT102 and HUT78 cancer cells, while they were minimally cytotoxic to the HEK-293 and LLC-PK1 normal cell lines. All the compounds were screened for cytotoxicity using MTT assay. Overall, these findings suggest that new benzopyran-2-one-triazole hybrid compounds, particularly FE-e, FE-f, FE-o and FE-q, exhibited promising cytotoxic activity mediated via inhibition of cancer cell proliferation and induction of apoptosis across these cancer cell lines. Additionally, these are selective anticancer agents, potentially safe for human cells, and could be synthesized at low cost.
Downloads
Metrics
References
Hemantha HP, Ramanujam R, Majeed M, Nagabhushanam K. An unambiguous and practical synthesis of Oroxylin A: a commonly misidentified flavone. Nat Prod Res. 2019;35(9):1413-1420. https://doi.org/10.1080/14786419.2019.1650359.
Husain A, Rashid M, Mishra R, Kumar D. Bis-chalcones and flavones: synthesis and antimicrobial activity. Acta Pol Pharm. 2013;70(3):443-9.
Brinkworth RI, Stoermer MJ, Fairlie DP. Flavones are inhibitors of HIV-1 proteinase. Biochem Biophys Res Commun. 1992;188(2):631-7. https://doi.org/10.1016/0006-291X(92)91103-W.
Gao L, Yang Z, Xiong J, Hao C, Ma R, Liu X, Liu BF, Jin J, Zhang G, Chen Y. Design, Synthesis and Biological Investigation of Flavone Derivatives as Potential Multi-Receptor Atypical Antipsychotics. Molecules. 2020;25(18):4107. https://doi.org/10.3390/molecules25184107.
Cheng J, Kondo K, Suzuki Y, Ikeda Y, Meng X, Umemura K. Inhibitory effects of total flavones of Hippophae Rhamnoides L on thrombosis in mouse femoral artery and in vitro platelet aggregation. Life Sci. 2003;72(20):2263-71. https://doi.org/10.1016/S0024-3205(03)00114-0.
Suetsugi M, Su L, Karlsberg K, Yuan YC, Chen S. Flavone and isoflavone phytoestrogens are agonists of estrogen-related. Mol Cancer Res. 2003;1(13):981-91.
Thillainayagam M, Malathi K, Ramaiah S. In-Silico molecular docking and simulation studies on novel chalcone and flavone hybrid derivatives with 1, 2, 3-triazole linkage as vital inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase. J Biomol Struct Dyn. 2018;36(15):3993-4009. DOI: 10.1080/07391102.2017.1404935
Zhang P, Wang Y, Zhang J, Maddock S, Snook M, Peterson T. A maize QTL for silk maysin levels contains duplicated Myb-homologous genes which jointly regulate flavone biosynthesis. Plant Mol Biol. 2003;52(1):1-5. https://doi.org/10.1023/A:1023942819106.
Chirumbolo S. The role of quercetin, flavonols and flavones in modulating inflammatory cell function. Inflamm Allergy Drug Targets. 2010;9(4):263-85. DOI: 10.2174/187152810793358741
De Matos AM, Martins A, Man T, Evans D, Walter M, Oliveira MC, López Ó, Fernandez-Bolaños JG, Dätwyler P, Ernst B, Macedo MP. Design and synthesis of CNS-targeted flavones and analogues with neuroprotective potential against H2O2-and Aβ1-42-induced toxicity in SH-SY5Y human neuroblastoma cells. Pharmaceuticals. 2019;12(2):98. https://doi.org/10.3390/ph12020098.
Kulkarni P, Wagh P, Zubaidha P. An improved and eco-friendly method for the synthesis of flavanone by the cyclization of 2’-hydroxy chalcone using methane sulphonic acid as catalyst. Chem J. 2012;2(3):106-10.
Zhang H, Yanagihara N, Toyohira Y, Takahashi K, Inagaki H, Satoh N, Li X, Goa X, Tsutsui M, Takahaishi, K. Stimulatory effect of nobiletin, a citrus polymethoxy flavone, on catecholamine synthesis through Ser 19 and Ser 40 phosphorylation of tyrosine hydroxylase in cultured bovine adrenal medullary cells. Naunyn-Schmiedeberg's Arch Pharmacol. 2014;387(1),15-22. DOI:10.1007/s00210-013-0916-6.
Horie T, Kawamura Y, Yamamoto H, Kitou T, Yamashita K. Synthesis of 5,8-dihydroxy-6,7-dimethoxyflavones and revised structures for some natural flavones. Phytochemistry.1995; 39(5): 1201-1210. https://doi.org/10.1016/0031-9422(95)00070-N.
Hasan SM, Alam MM, Husain A, Khanna S, Akhtar M, Zaman MS. Synthesis of 6-aminomethyl derivatives of benzopyran-4-one with dual biological properties: anti-inflammatory-analgesic and antimicrobial. Eur J Med Chem. 2009;44(12):4896-903. https://doi.org/10.1016/j.ejmech.2009.08.001.
Shingo Sato S, Akiya T, Nishizawa H, Suzuki T. Total synthesis of three naturally occurring 6,8-di-C-glycosylflavonoids: phloretin, naringenin, and apigenin bis-C-β-D-glucosides. Carbohydrate Res. 2006;341(8):964-970. https://doi.org/10.1016/j.carres.2006.02.019.
Zangade SB, Jadhaqv JD, Vibhute YB, Dawane BS. Synthesis and antimicrobial activity of some new chalcones and flavones. J Chem Pharm Res. 2010;2(1):310-314.
Zheng X, Meng WD, Xu YY, Cao JG, Qing FL. Synthesis and anticancer effect of chrysin derivatives. Bioorg Med Chem Lett. 2003 Mar 10;13(5):881-4.
YerraKoteswaraRaoetal.Synthesisandcellcycleevaluationsofnovelflavonoidderivatives.BioorgMed Chem 2005; 13: 6850-6855. https://doi.org/10.1016/S0960-894X(02)01081-8.
Vatkar BS, Pratapwar AS, Tapas AR, Butle SR, Tiwari B. Synthesis and antimicrobial activity of some flavanone derivatives. Int J Chem Tech Res. 2010; 2(1): 504-508.
Chimenti F, Fioravanti R, Bolasco A, Chimenti P, Secci D, Rossi F, Yáñez M, Orallo F, Ortuso F, Alcaro S, Cirilli R, Ferretti R, Sanna ML. A new series of flavones, thioflavones, and flavanones as selective monoamine oxidase-B inhibitors. Bioorg Med Chem. 2010;18(3):1273-9. https://doi.org/10.1016/j.bmc.2009.12.029.
Alam S, Mostahar S. Studies of antimicrobial activity of two synthetic 2,4,6-trioxygenated flavones. J Applied Sci. 2005;5(2): 327-333. https://scialert.net/abstract/?doi=jas.2005.327.333
Menezes MJ, Manjrekar S, Pai V, Patre RE, Tilve SG. A facile microwave assisted synthesis of flavones. Ind J Chem. 2009;48:1311-1314.
Sohel M, Alam MS, Islam A. Cytotoxic and antimicrobial activities of two new synthetic 2-oxygenated flavones reported from andrographis viscosula. J Serb Chem Soc. 2006;72(4):321-329. https://doi.org/10.2298/JSC0704321M.
Mokle SS, Vibhute YB. Synthesis of some new biologically active chalcones and flavones. Der Pharma Chemica. 2009;1(2):145-152.
Lincy J, Mathew G. Preliminary screening of pharmacological activities of E-3 arylidene flavanones. J Basic Appl Sci. 2010; 6(2): 135-139.
Prasad YR, Atmakuri LR, Rambabu Rl. Synthesis and antimicrobial activity of some chalcones derivatives. E-J Chem 2008;5(3):461-466.
Cabrera M, Simoens M, Falchi G, Lavaggi ML, Piro OE, Castellano EE, Vidal A, Azqueta A, Monge A, de Ceráin AL, Sagrera G, Seoane G, Cerecetto H, González M. Synthetic chalcones, flavanones, and flavones as antitumoral agents: biological evaluation and structure-activity relationships. Bio org Med Chem. 2007;15(10):3356-67. https://doi.org/10.1016/j.bmc.2007.03.031.
Huang WH, Chien PY, Yang CH, Lee AR. Novel synthesis of flavonoids of Scutellaria baicalensis georgi. Chem Pharm Bull. 2003;51(3): 339-340. https://doi.org/10.1248/cpb.51.339.
Gomes A, Neuwirth O, Freitas M, Couto D, Ribeiro D, Figueiredo AG, Silva AM, Seixas RS, Pinto DC, Tomé AC, Cavaleiro JA, Fernandes E, Lima JL. Synthesis and antioxidant properties of new chromone derivatives. Bioorg Med Chem. 2009;17(20):7218-26. https://doi.org/10.1016/j.bmc.2009.08.056.
Tang L, Zhang S, Yang J, Gao W, Cui J, Zhuang T. A novel approach to the synthesis of 6-amino-7-hydroxy-flavone. Molecules. 2004;9:842-848. https://doi.org/10.3390/91000842.
Lee JI, Son HS, Park H. An efficient synthesis of flavones from 2-hydroxy benzoic acids. Bull Korean Chem Soc. 2004;25(12):1945-1947. https://doi.org/10.5012/bkcs.2004.25.12.1945b
Kumazawa T, Kimura T, Matsuba S, Sato S, Onodera J. Synthesis of 8-C-glucosylflavones. Carbohydr Res. 2001 Aug 30;334(3):183-93. https://doi.org/10.1016/S0008-6215(01)00192-6
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
You are free to:
- Share — copy and redistribute the material in any medium or format
- Adapt — remix, transform, and build upon the material for any purpose, even commercially.
Terms:
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
