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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Design, Synthesis, and Antiproliferative Activity of Novel Flavone Derivatives

Author(s): Lata C. Potey*, Prafulla M. Sabale and Vidya P. Sabale

Volume 20, Issue 10, 2023

Published on: 28 October, 2022

Page: [1610 - 1620] Pages: 11

DOI: 10.2174/1570180819666220919124717

Price: $65

Abstract

Background: Cancer is a complex disease in which some of the cells grow uncontrollably and spread to other parts of the body.

Objective: The present study focuses on molecular docking and synthesis of novel flavone derivatives substituted with heterocyclic rings.

Methods: The anticancer activity of novel flavones against human aromatase enzyme using human breast cancer cell line MCF-7 through MTT assay was demonstrated. The synthesized compounds for the determination of single or double-strand DNA damage through the single-cell electrophoresis/comet assay were evaluated.

Results: In this study, we found that the derivative 3M with morpholine ring showed the highest anticancer potency against the MCF-7 cell line compared to that of other flavone derivatives. Compound 3T showed less cytotoxicity against the MCF-7 cell line.

Conclusion: Based on the findings, flavone scaffolds can be selected as a skeleton for the development of heterocyclic amine-containing flavones with the potential to develop as anticancer drugs.

Keywords: Flavones, cancer, breast cancer, MCF-7, cytotoxicity, Comet assay, MTT assay

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Graphical Abstract

[1]
Kshatriya, R.; Shaikh, Y.; Nazeruddin, G. Synthesis of flavone skeleton by different methods. Orient. J. Chem., 2013, 29(4), 1475-1487.
[http://dx.doi.org/10.13005/ojc/290425]
[2]
Albogami, A.S.; Karama, U.; Amine Mousa, A.; Khan, M.; Al-Mazroa, S.A.; Alkhathlan, H.Z. Simple and efficient one step synthesis of functionalized flavanones and chalcones. Orient. J. Chem., 2012, 28(2), 619-626.
[http://dx.doi.org/10.13005/ojc/280201]
[3]
Jyothi, N.R.; Farook, N.A.; Lakshmi, D.V.; Yadav, P.S. Anti-fungal activities of thiosemicarbazones and their copper (II) complexes. Pharmacophore, 2019, 10(4), 1-7.
[4]
Mathew, S.; Victório, C.P. Antifungal properties of rhizomes of Alpiniacalcarata roscoe from Western Ghats. South India. Int. J. Pharm. Phytopharm. Res., 2020, 10(5), 1-7.
[5]
Vosooghi, M.; Firoozpour, L.; Rodaki, A.; Pordeli, M.; Safavi, M.; Ardestani, S.K.; Dadgar, A.; Asadipour, A.; Moshafi, M.H.; Foroumadi, A. Design, synthesis, docking study and cytotoxic activity evaluation of some novel letrozole analogs. Daru, 2014, 22(1), 83.
[http://dx.doi.org/10.1186/s40199-014-0083-4] [PMID: 25539909]
[6]
Balunas, M.; Su, B.; Brueggemeier, R.; Kinghorn, A. Natural products as aromatase inhibitors. Anticancer. Agents Med. Chem., 2008, 8(6), 646-682.
[http://dx.doi.org/10.2174/187152008785133092] [PMID: 18690828]
[7]
Kabalka, G.W.; Mereddy, A.R. Microwave-assisted synthesis of functionalized flavones and chromones. Tetrahedron Lett., 2005, 46(37), 6315-6317.
[http://dx.doi.org/10.1016/j.tetlet.2005.07.038]
[8]
Vyskočil, Š.; Jaracz, S.; Smrčina, M.; Štícha, M.; Hanuš, V.; Polášek, M.; Kočovský, P. Synthesis of N-Alkylated and N-Arylated Derivatives of 2-Amino-2‘-hydroxy-1,1‘-binaphthyl (NOBIN) and 2,2‘-Diamino-1,1‘-binaphthyl and their application in the enantioselective addition of diethylzinc to aromatic aldehydes. J. Org. Chem., 1998, 63(22), 7727-7737.
[http://dx.doi.org/10.1021/jo9807565]
[9]
Nguyen, L.T.; Lee, Y.H.; Sharma, A.R.; Park, J.B.; Jagga, S.; Sharma, G.; Lee, S.S.; Nam, J.S. Quercetin induces apoptosis and cell cycle arrest in triple-negative breast cancer cells through modulation of Foxo3a activity. Korean J. Physiol. Pharmacol., 2017, 21(2), 205-213.
[http://dx.doi.org/10.4196/kjpp.2017.21.2.205] [PMID: 28280414]
[10]
Recanatini, M.; Cavalli, A.; Valenti, P. Nonsteroidal aromatase inhibitors: Recent advances. Med. Res. Rev., 2002, 22(3), 282-304.
[http://dx.doi.org/10.1002/med.10010] [PMID: 11933021]
[11]
Richie, R.C.; Swanson, J.O. Breast cancer: A review of the literature. J. Insur. Med., 2003, 35(2), 85-101.
[PMID: 14733031]
[12]
Kumar, S.; Pandey, A.K. Chemistry and biological activities of flavonoids: An overview. ScientificWorldJournal, 2013, 2013, 1-16.
[http://dx.doi.org/10.1155/2013/162750] [PMID: 24470791]
[13]
Sgrignani, J.; Cavalli, A.; Colombo, G.; Magistrato, A. Enzymatic and inhibition mechanism of human aromatase (CYP19A1) enzyme. A computational perspective from QM/MM and classical molecular dynamics simulations. Mini Rev. Med. Chem., 2016, 16(14), 1112-1124.
[http://dx.doi.org/10.2174/1389557516666160623101129] [PMID: 27337972]
[14]
Smith, I.E.; Dowsett, M. Aromatase inhibitors in breast cancer. N. Engl. J. Med., 2003, 348(24), 2431-2442.
[http://dx.doi.org/10.1056/NEJMra023246] [PMID: 12802030]
[15]
Schofield, C.A.; Dea Moore, C.; Hall, A.; Coles, M.E. Understanding perceptions of anxiety disorders and their treatment. J. Nerv. Ment. Dis., 2016, 204(2), 116-122.
[http://dx.doi.org/10.1097/NMD.0000000000000433] [PMID: 26669982]
[16]
Baum, M.; Buzdar, A. The current status of aromatase inhibitors in the management of breast cancer. Surg. Clin. North Am., 2003, 83(4), 973-994.
[http://dx.doi.org/10.1016/S0039-6109(03)00031-8] [PMID: 12875605]
[17]
Nadin, S.B.; Vargas-Roig, L.M.; Ciocca, D.R. A silver staining method for single-cell gel assay. J. Histochem. Cytochem., 2001, 49(9), 1183-1186.
[http://dx.doi.org/10.1177/002215540104900912] [PMID: 11511687]
[18]
Ostling, O.; Johanson, K.J. Microelectrophoretic study of radiation-induced DNA damages in individual mammalian cells. Biochem. Biophys. Res. Commun., 1984, 123(1), 291-298.
[http://dx.doi.org/10.1016/0006-291X(84)90411-X] [PMID: 6477583]
[19]
Singh, N.P.; McCoy, M.T.; Tice, R.R.; Schneider, E.L. A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell Res., 1988, 175(1), 184-191.
[http://dx.doi.org/10.1016/0014-4827(88)90265-0] [PMID: 3345800]
[20]
Choucroun, P.; Gillet, D.; Dorange, G.; Sawicki, B.; Dewitte, J.D. Comet assay and early apoptosis. Mutat. Res., 2001, 478(1-2), 89-96.
[http://dx.doi.org/10.1016/S0027-5107(01)00123-3] [PMID: 11406173]

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