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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

Synthesis and Docking Study of Some Bioactive N-(benzo[d]thiazol-2-yl)- 2-(4-((substituted)phenoxy)acetamide on Cyclo-oxygenase-2 Enzyme and In vivo Analgesic Activity Evaluation

Author(s): Sumit Kumar, Arvind Kumar*, Amit Verma and Arun Kumar Mishra*

Volume 18, Issue 4, 2021

Published on: 22 October, 2020

Page: [396 - 405] Pages: 10

DOI: 10.2174/1570180817999201022193901

Price: $65

Abstract

Background: The benzothiazole and its derivatives reported an extremely crucial duty in the progress of commercially important intermediary molecules, which are wanted for the manufacturing of various pharmacologically active agents.

Introduction: As a necessary element of ongoing examination for the synthesis of new nonsteroidal anti-inflammatory agents (NSAIDs), a number of new benzothiazole derivatives were taken under consideration for the synthesis and were computationally studied along with their biological activity.

Methods: Obtainable benzothiazole derivatives were synthesized by the condensing of 2-(4- aminophenoxy)-N-(benzo[d]thiazol-2-yl)acetamide with substituted acetophenones in ethanol in the presence of a catalytic amount of glacial acetic acid. The structures of newly synthesized compounds were characterized by IR, NMR spectroscopy and elemental analysis techniques. Several molecular properties of these derivatives were computed in order to estimate their drug like candidates. Molecular docking was performed to these synthesized derivatives with particular reference to cyclooxygenase-2 (COX-2) enzyme. The synthesized derivatives were screened for their biological activity, including analgesic and anti-inflammatory activity as COX-2 inhibitors.

Results: From all data, it established that among all target compounds, S-4 (N-(benzo[d]thiazol- 2-yl)-2-(4-((1-(3-nitrophenyl)ethylidene)amino)phenoxy)acetamide) displayed the highest antiinflammatory and analgesic effects.

Conclusion: All these findings recommended that S-4 might be utilized as a promising new lead compound for Nonsteroidal anti-inflammatory drug (NSAIDs) development.

Keywords: Indole, molecular docking, analgesic activity, anti-inflammatory activity, benzothiazole, biological activity.

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[1]
Cioli, V.; Putzolu, S.; Rossi, V.; Scorza Barcellona, P.; Corradino, C. The role of direct tissue contact in the production of gastrointestinal ulcers by anti-inflammatory drugs in rats. Toxicol. Appl. Pharmacol., 1979, 50(2), 283-289.
[http://dx.doi.org/10.1016/0041-008X(79)90153-4] [PMID: 505458]
[2]
Kameshwar, V.H. R, K.J.; Priya, B.S.; Swamy, S.N. Synthesis, characterization and bioactivity studies of novel 1,3,4-oxadiazole small molecule that targets basic phospholipase A2 from Vipera russelli. Mol. Cell. Biochem., 2017, 426(1-2), 161-175.
[http://dx.doi.org/10.1007/s11010-016-2888-6] [PMID: 27928710]
[3]
Deodhar, M.N.; Dongre, A.C.; Kudale, S.D. Analgesic and antiinflammatory activity of derivatives of 2-aminobenzothiazole. Asian J. Chem., 2012, 24(6), 2747-2752.
[4]
Martins, P.; Jesus, J.; Santos, S.; Raposo, L.R.; Roma-Rodrigues, C.; Baptista, P.V.; Fernandes, A.R. Heterocyclic anticancer compounds: recent advances and the paradigm shift towards the use of nanomedicine’s tool box. Molecules, 2015, 20(9), 16852-16891.
[http://dx.doi.org/10.3390/molecules200916852] [PMID: 26389876]
[5]
Khokra, S.L.; Arora, K.; Mehta, H.; Aggarwal, A.; Yadav, M. Common methods to synthesize benzothiazole derivatives and their medicinal significance: A review. Int. J. Pharm. Sci. Res., 2011, 2(6), 1356-1377.
[6]
Wilson, K.; Chissick, H.; Fowler, A.M.; Frearson, F.J.; Gittins, M.; Swinbourne, F.J. Metabolism of benzothiazole. I. Identification of ring-cleavage products. Xenobiotica, 1991, 21(9), 1179-1183.
[http://dx.doi.org/10.3109/00498259109039558] [PMID: 1788986]
[7]
Seth, S. A Comprehensive review on recent advances in synthesis & pharmacotherapeutic potential of benzothiazoles. Antiinflamm. Antiallergy Agents Med. Chem., 2015, 14(2), 98-112.
[http://dx.doi.org/10.2174/1871523014666150528110703] [PMID: 26017385]
[8]
Prajapat, P. Importance of benzothiazole motif in modern drug discovery. Introduction. Mod. Appro. Drug Des., 2018, 1(4), 1-2.
[9]
Bozec, L.L.; Moody, C.J. Aust. J. Chem., 2009, 62, 639-647.
[http://dx.doi.org/10.1071/CH09126]
[10]
Deshmukh, R.; Thakur, A.S.; Jha, A.K.; Deshmukh, R. synthesis and biological evaluation of some 1, 3-benzthiazoles derivatives. Int. J. Res. Pharm. Chem., 2011, 1, 329-333.
[11]
Liu, D.C.; Zhang, H.J.; Jin, C.M.; Quan, Z.S. Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticonvulsant agents. Molecules, 2016, 21(3), 164.
[http://dx.doi.org/10.3390/molecules21030164] [PMID: 26938519]
[12]
Verma, A.K.; Martin, A.; Singh, A.K. Characterization and evaluation of anti-inflammatory and analgesic activity of benzothiazole derivatives. Ind. J. Pharm. Biol. Res., 2014, 2, 84-89.
[http://dx.doi.org/10.30750/ijpbr.2.3.14]
[13]
Pathak, N.; Rathi, E. Kumar. N.; Kini. S.G.; Rao. M. A review on anticancer potentials of benzothiazole derivatives. Mini Rev. Med. Chem., 2020, 20(1), 12-23.
[http://dx.doi.org/10.2174/1389557519666190617153213] [PMID: 31288719]
[14]
Özkay, D.; Kaya, C.; Acar, Ç.U.; Can, Ö.D. Synthesis and antidepressant activity profile of some novel benzothiazole derivatives. Molecules, 2017, 22, 1490.
[http://dx.doi.org/10.3390/molecules22091490]
[15]
Takahashi, S.; Kano, H. Studies of heteroaromatic N-oxides. IX. The synthesis and structure of benzothiazole N-oxides. Chem. Pharm. Bull. (Tokyo), 1969, 17, 1598-1604.
[http://dx.doi.org/10.1248/cpb.17.1598]
[16]
Hutchinson, I.; Stevens, M.F.G.; Westwel, A.D. The regiospecific synthesis of 5- and 7-monosubstituted and 5,6-disubstituted 2-arylbenzothiazoles. Tetrahedron Lett., 2000, 41, 425-428.
[http://dx.doi.org/10.1016/S0040-4039(99)02076-6]
[17]
Tale, R.H. Novel synthesis of 2-arylbenzothiazoles mediated by ceric ammonium nitrate (CAN). Org. Lett., 2002, 4(10), 1641-1642.
[http://dx.doi.org/10.1021/ol020027i] [PMID: 12000262]
[18]
Iwan, A.; Siwy, M.; Janeczek, H.; Rannou, P. Synthesis and mesomorphism of 2,5-bis(3,4-bis(n-alkoxy)phenyl)thiazolo[5,4-d]thiazole tetracatenar liquid crystals. Phase Transit., 2012, 85, 297-308.
[http://dx.doi.org/10.1080/01411594.2011.646266]
[19]
Kumar, S.; Pandey, P.; Srivastava, Y.; Kumar, A. Synthesis, computational studies and pharmacological evaluation of some acetamides as serotonin antagonists. Pharma Chem., 2011, 3(4), 195-200.
[20]
Karlgren, M.; Bergstrom, C.A.S. New horizons in predictive drug metabolism and pharmacokinetics, 2015., 1-26..
[21]
Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31(2), 455-461.
[PMID: 19499576]
[22]
OCED/OCDC. OCED/OCDC.OECD guidelines for testing of chemicals Revised draft guidelines 423, acute oral toxicity class method, 2000..
[23]
Eddy, N.B.; Leimbach, D. Synthetic analgesics. II. Dithienylbutenyl- and dithienylbutylamines. J. Pharmacol. Exp. Ther., 1953, 107(3), 385-393.
[PMID: 13035677]
[24]
Winter, C.A.; Risley, E.A.; Nuss, G.W. Carrageenin-induced edema in hind paw of the rat as an assay for antiiflammatory drugs. Proc. Soc. Exp. Biol. Med., 1962, 111, 544-547.
[http://dx.doi.org/10.3181/00379727-111-27849] [PMID: 14001233]
[25]
Khan, M.T.H.; Sylte, I. Predictive QSAR modeling for the successful predictions of the ADMET properties of candidate drug molecules. Curr. Drug Discov. Technol., 2007, 4(3), 141-149.
[http://dx.doi.org/10.2174/157016307782109706] [PMID: 17985997]
[26]
Pantsar, T.; Poso, A. Binding affinity via docking: Fast and fiction. Molecules 2018, 23(1899), 1-11.,
[http://dx.doi.org/10.3390/molecules23081899]
[27]
Smith, W.L.; Dewitt, D.L. Prostaglandin endoperoxide H synthases-1 and -2. Adv. Immunol., 1996, 62, 167-215.

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