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Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

General Research Article

Design and Synthesis of Novel Coumarin Conjugated Acetamides as Promising Anticancer Agents: An In Silico and In Vitro Approach

Author(s): S.V. Mamatha*, Shiddappa L. Belagali, Mahesh Bhat and Vijay M. Kumbar

Volume 21, Issue 11, 2021

Published on: 14 July, 2020

Page: [1431 - 1440] Pages: 10

DOI: 10.2174/1871520620666200714140820

Price: $65

Abstract

Background: Coumarin and benzophenone possess a vast sphere of biological activities, whereas thiazoles display various pharmacological properties. Hence, present study focused on the incorporation of coumarin and thiazole core to the benzophenone skeleton to enhance the bioactivity, anticipating their interesting biological properties.

Objective: The objective of the current work is the synthesis and biological evaluation of a novel series of coumarin fused thiazole derivatives.

Methods: A novel series of coumarin conjugated thiazolyl acetamide hybrid derivatives were synthesized by a multistep reaction sequence and were characterized by the FT-IR, LCMS, and NMR spectral techniques. The newly synthesized compounds were screened for anti-cancer activity by in silico and in vitro methods. The cytotoxicity of the synthesized unique compounds was executed for two different cancer cell lines, MCF-7 (Breast cancer) and KB (Oral cancer), in comparison with standard paclitaxel by MTT assay.

Results: The compound 7f is a potent motif with an acceptable range of IC50 values, for anti-cancer activity, i.e., 63.54μg/ml and 55.67μg/ml, against the MCF-7 and KB cell lines, respectively. Molecule docking model revealed that this compound formed three conventional hydrogen bonds with the active sites of the amino acids, MET 769, ARG 817, and LYS 721.

Conclusion: Compound 7f with two methyl groups on the phenoxy ring and one 4-position methoxy group on the benzoyl ring, showed a significant cytotoxic effect. An advantageous level of low toxicity against normal cell line (L292) by MTT assay was determined.

Keywords: Coumarin, acetamides, thiazole, anti-cancer, benzophenone, in silico.

Graphical Abstract
[1]
Henry Jacobs, G.E.; Carrington, C.M.S.; McLean, S.; Freeholds, W. Prenylated benzophenone derivatives from Caribbean clusia species (guttiferae). Plukenetiones BeG and xerophenone A. Tetrahedron, 1999, 55, 1581-1596.
[http://dx.doi.org/10.1016/S0040-4020(98)01203-4]
[2]
Kumazawa, E.; Hirotani, K.; Burford, S.C.; Kawagoe, K.; Miwa, T.; Mitsui, I.; Ejima, A. Synthesis and antitumor activity of novel benzophenone derivatives. Chem. Pharm. Bull. (Tokyo), 1997, 45(9), 1470-1474.
[http://dx.doi.org/10.1248/cpb.45.1470] [PMID: 9331999]
[3]
El-Sabbagh, O.I.; Baraka, M.M.; Ibrahim, S.M.; Pannecouque, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; Rashad, A.A. Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur. J. Med. Chem., 2009, 44, 3746-3753.
[http://dx.doi.org/10.1016/j.ejmech.2009.03.038] [PMID: 19419804]
[4]
Zaharia, V.; Ignat, A.; Palibroda, N.; Ngameni, B.; Kuete, V.; Fokunang, C.N.; Moungang, M.L.; Ngadjui, B.T. Synthesis of some p-toluenesulfonyl-hydrazinothiazoles and hydrazino-bis-thiazoles and their anticancer activity. Eur. J. Med. Chem., 2010, 45, 5080-5085.
[http://dx.doi.org/10.1016/j.ejmech.2010.08.017] [PMID: 20810194]
[5]
Hutchinson, I.; Jennings, S.A.; Vishnuvajjala, B.R.; Westwell, A.D.; Stevens, M.F.G. Antitumor benzothiazoles. 16. Synthesis and pharmaceutical properties of antitumor 2-(4-aminophenyl) benzothiazole amino acid prodrugs. J. Med. Chem., 2002, 45, 744-747.
[http://dx.doi.org/10.1021/jm011025r] [PMID: 11806726]
[6]
Ulusoy, N.; Kiraz, M.; Kucukbasmaci, O. New 6-(4-Bromophenyl)-imidazo[2,1-b]thiazole derivatives: Synthesis and antimicrobial activity. Monatsh. Chem., 2002, 133, 1305.
[http://dx.doi.org/10.1007/s007060200108]
[7]
Kaplancikli, Z.A.; Zitouni, G.T.; Revial, G.; Guven, K. Synthesis and study of antibacterial and antifungal activities of novel 2-[[(benzoxazole/benzimidazole-2-yl)sulfanyl] acetylamino] thiazoles. Arch. Pharm. Res., 2004, 27, 1081.
[http://dx.doi.org/10.1007/BF02975108] [PMID: 15595406]
[8]
Al-Saddi, M.S.; Faidallah, H.M.; Rostom, S.A.F. Synthesis and Antimicrobial Study of Novel 1-Aryl-2-oxo-indano[3,2-d]pyrido/pyrimido[1,2-b]pyrimidines. Arch. Pharm. Chem. Life Sci., 2008, 341(7), 418-423.
[9]
Kirkiacharian, B.S.; Clercq, E.; Kurkjian, R.; Pannecouque, C. New synthesis and anti-HIV and antiviral properties of 3-arylsulfonyl derivatives of 4-hydroxycoumarin and 4- hydroxyquinolone. J. Pharm. Chem., 2008, 42, 265-270.
[http://dx.doi.org/10.1007/s11094-008-0103-0]
[10]
Adami, E.; Marazzi-Uberti, E.; Turba, C. Analgesic action of 4-hydroxycoumarin. Arch. Ital. Sci. Farmacol., 1959, 9, 61-69.
[PMID: 13650911]
[11]
Chiarino, D.; Grancini, G.C.; Frigeni, V.; Carenzi, A. Preparation and formulation of 4- (3-coumarinyl)thiazole derivatives with antiallergic, antianaphylactic and antiarthritic activity. US Patent 902,688A, 1987.
[12]
Luchini, A.C.; Rodrigues-Orsi, P.; Cestari, S.H.; Seito, L.N.; Witaicenis, A.; Pellizzon, C.H.; Di Stasi, L.C. Intestinal anti-inflammatory activity of coumarin and 4-hydroxycoumarin in the trinitrobenzenesulphonic acid model of rat colitis. Biol. Pharm. Bull., 2008, 31(7), 1343-1350.
[http://dx.doi.org/10.1248/bpb.31.1343] [PMID: 18591772]
[13]
Stern, P.; Dezelic, M.; Kosak, R. Analgetic and antipyretic action of vitamin K and dicoumarol with special consideration of 4-hydroxycoumarin. Naunyn Schmiedebergs Arch. Exp. Pathol. Pharmakol., 1957, 232, 356-359.
[http://dx.doi.org/10.1007/BF00259919] [PMID: 13526895]
[14]
Chohan, Z.H.; Shaikh, A.U.; Rauf, A.; Supuran, C.T. Antibacterial, antifungal and cytotoxic properties of novel N-substituted sulfonamides from 4-hydroxycoumarin. J. Enzyme Inhib. Med. Chem., 2006, 21(6), 741-748.
[http://dx.doi.org/10.1080/14756360600810340] [PMID: 17252948]
[15]
Govindhan, M.; Subramanian, K.; Chennakesava Rao, K.; Easwaramoorthi, K.; Senthil Kumar, P.; Perumal, P.T. Synthesis of novel 4-hydroxycoumarin derivatives: Evaluation of antimicrobial, antioxidant activities and its molecular docking studies. Med. Chem. Res., 2015, 24, 4181-4190.
[http://dx.doi.org/10.1007/s00044-015-1448-z]
[16]
Abdul Amir, H.K.; Al-Amiery, A.A.; Ahmed, Y.M.; Abu Bakar, M. The antioxidant activity of new coumarin derivatives. J. Mol. Sci, 2011, 12, 5747-5761.
[http://dx.doi.org/10.3390/ijms12095747]
[17]
Shapiro, S.; Sherwin, B.; Thromboembolization, I.I. The use of dicoumarol (3,3′- methylenebis (4- hydroxycoumarin) in embolization. Report of five cases. N. Y. State J. Med., 1943, 43, 45-52.
[18]
Butsch, W.L.; Stewart, J.D. Administration of dicoumarin compound for prophylaxis of postoperative thrombosis and embolism. Arch. Surg., 1942, 45, 551-553.
[http://dx.doi.org/10.1001/archsurg.1942.01220040047005]
[19]
Hintz, K.K.; Ren, J. Tetramethylpyrazine elicits disparate responses in cardiac contraction and intracellular Ca(2+) transients in isolated adult rat ventricular myocytes. Vascul. Pharmacol., 2003, 40(4), 213-217.
[http://dx.doi.org/10.1016/j.vph.2003.08.002] [PMID: 14746828]
[20]
Arshad, A.; Osman, H.; Bagley, M.C.; Lam, C.K.; Mohamad, S.; Zahariluddin, A.S.M. Synthesis and antimicrobial properties of some new thiazolyl coumarin derivatives. Eur. J. Med. Chem., 2011, 46, 3788-3794.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.044] [PMID: 21712145]
[21]
Vijesh, A.M.; Isloor, A.M.; Prabhu, V.; Ahmad, S.; Malladi, S. Synthesis, characterization and anti-microbial studies of some novel 2,4-disubstituted thiazoles. Eur. J. Med. Chem., 2010, 45, 5460-5464.
[http://dx.doi.org/10.1016/j.ejmech.2010.07.048] [PMID: 20716467]
[22]
Siddiqui, N.; Arshad, M.; Khan, S.A. Synthesis of some new coumarin incorporated thiazolyl semicarbazones as anticonvulsants. Acta Pol. Pharm. Drug Res., 2009, 66, 161-167.
[23]
Kalkhambkar, R.; Kulkarni, G.; Shivkumar, H.; Rao, R. Synthesis of novel triheterocyclic thiazoles as anti-inflammatory and analgesic agents. Eur. J. Med. Chem., 2007, 42, 1272-1276.
[http://dx.doi.org/10.1016/j.ejmech.2007.01.023] [PMID: 17337096]
[24]
Yarden, Y.; Sliwkowski, M.X. Untangling the ErbB signalling network. Nat. Rev. Mol. Cell. Biol., 2001, 2, 127-137.
[25]
Arteaga, C.L. The epidermal growth factor receptor: From mutant oncogene in nonhuman cancers to therapeutic target in human neoplasia. J. Clin. Oncol., 2001, 19(18)(Suppl.), 32S-40S.
[PMID: 11560969]
[26]
Ellis, L.M. Epidermal growth factor receptor in tumor angiogenesis. Hematol. Oncol. Clin. North Am., 2004, 18(5), 1007-1021.
[http://dx.doi.org/10.1016/j.hoc.2004.06.002] [PMID: 15474332]
[27]
Sahin, O.; Ozdemir, U.O.; Seferoglu, N.; Aydiner, B.; Sari, M.; Tunc, T.; Seferoglu, Z. A highly selective and sensitive chemosensor derived coumarin-thiazole for colorimetric and fluorimetric detection of CN− ion in DMSO and aqueous solution: Synthesis, sensing ability, Pd(II)/Pt(II) complexes and theoretical studies. Tetrahedron, 2016, 72, 5843-5852.
[http://dx.doi.org/10.1016/j.tet.2016.08.004]
[28]
Mamatha, S.V.; Mahesh, B.; Sagar, B.K.; Meenakshi, S.K. Synthesis, characterization, crystal structure biological activity of 4-{2-[5-(4-fluoro-phenyl)- [1,3,4]oxadiazol-2-ylsulfanyl]-ethyl}-morpholine. J. Mol. Struct., 2019, 1196, 186-193.
[29]
RSCB Protein Data Bank. www.rcsb.org/pdb
[30]
Bhat, M.; Belagali, S.L. Synthesis, characterization and biological screening of pyrazole-conjugated benzothiazole analogs. Future Med. Chem., 2017, 10(1), 71-87.
[http://dx.doi.org/10.4155/fmc-2017-0138] [PMID: 29235357]
[31]
Bhat, S.S.; Revankar, V.K.; Kumbar, V.; Bhat, K.; Kawade, V.A. Synthesis, crystal structure and biological properties of a cis-dichloridobis(diimine)copper(II) complex. Acta Crystallogr., 2018, 74, 146-151.
[32]
Mamatha, S.V.; Belagali, S.L.; Mahesh, B. Med. Drug. Dis., 2019, 3(100017), 1-9.
[33]
Mamatha, S.V.; Mahesh Bhat, H.K.; Kumara, D.; Channe Gowda, S.K. Meenakshi. Chemical data. Collections, 2020, 20, 100343.

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