Design, synthesis and evaluation of anti-inflammatory, analgesic and antibacterial activity of 2, 4, 6-trisubstituted quinazoline derivatives

Jain, Nivrati; Jain, Harshita; Jain, Ashish; Ravichandran, Veerasamy; Jain, Prateek

doi:10.2478/auoc-2018-0014

Abstract

We described here the synthesis and biological evaluation of a series of 2, 4, 6-trisubstituted quinazoline derivatives as potential anti-inflammatory, analgesic and antibacterial agents. The synthesized compounds were characterized by FTIR, 1H NMR and mass spectroscopy analysis. We found that the compounds 6b, 6e, 6g, 6h and 6j showed better anti-inflammatory activity than indomethacin. Compounds 6b, 6e, 6h, 6j and 6l were found to exhibit appreciable analgesic activity, and 6b, 6g and 6k showed good antibacterial activity against Gram (+) bacteria: B. subtilis, S. aureus, S. epidermis, and Gram (-) bacteria: E. coli, P. aeruginosa and K. pneumoniae. Compound 6b showed overall better anti-inflammatory, analgesic and antibacterial activity among the synthesized compounds. The results of the present study could be helpful for the designing of effective anti-inflammatory, analgesic and antibacterial agents.

References

[1]. B.L. SNG, S.A. Schug, The role of opioids in managing chronic non-cancer pain, Ann. Acad. Med. 38 (2009) 960 - 966.10.47102/annals-acadmedsg.V38N11p960
Search in Google Scholar Back to article
[2]. A.M. Jane, D.W. Timothy, Cyclo-oxygenase-2: pharmacology, physiology, biochemistry and relevance to NSAID therapy, Br. J. Pharmacol. 128 (1999) 1121-1132.10.1038/sj.bjp.0702897
Search in Google Scholar Back to article
[3]. J.R. Vane, Y.S. Bakhle, R.M. Botting, Cyclooxygenases 1 and 2, Ann. Rev. Pharmacol. Toxicol. 38 (1998) 97-120.10.1146/annurev.pharmtox.38.1.979597150
Search in Google Scholar Back to article
[4]. D.L. Simmons, R.M. Botting, T. Hla, Cyclooxygenase isozymes: The biology of prostaglandin synthesis and inhibition, Pharmacol. Rev. 56 (2004) 387 - 437.10.1124/pr.56.3.3
Search in Google Scholar Back to article
[5]. D. Adebayo, I. Bjarnason, Is non-steroidal anti-inflammaory drug (NSAID) enteropathy clinically more important than NSAID gastropathy?, Postgrad. Med. J. 82 (2006) 186 - 191.10.1136/pgmj.2005.039586256370816517800
Search in Google Scholar Back to article
[6]. S.C. Park, H.J. Chun, C.D. Kang, D. Sul, Prevention and management of non-steroidal anti-inflammatory drugs-induced small intestinal injury, World J. Gastroenterol. 17 (2011) 4647-4653.10.3748/wjg.v17.i42.4647323730122180706
Search in Google Scholar Back to article
[7]. A. Mishra, R. Veerasamy, P.K. Jain, V.K. Dixit, R.K. Agrawal, Synthesis, characterization and pharmacological evaluation of amide prodrugs of Flurbiprofen, J. Braz. Chem. Soc. 19 (2008) 89 - 100.10.1590/S0103-50532008000100014
Search in Google Scholar Back to article
[8]. A. Mishra, R. Veerasamy, P.K. Jain, V.K. Dixit, R.K. Agrawal, Synthesis, characterization and pharmacological evaluation of amide prodrugs of ketorolac, Eur. J. Med. Chem. 43 (2008) 2464 - 2472.10.1016/j.ejmech.2007.09.01117967497
Search in Google Scholar Back to article
[9]. P.M. Chandrika, T. Yakaiah, A.R.R. Rao, B. Narsaiah, N.C. Reddy, V. Sridhar, J.V.E. Rao, Synthesis of novel 4,6-disubstituted quinazoline derivatives, their anti-inflammatory and anti-cancer activity (cytotoxic) against U937 leukemia cell lines, Eur. J. Med. Chem. 43 (2008) 846 - 852.10.1016/j.ejmech.2007.06.01017689837
Search in Google Scholar Back to article
[10]. A.A. Farag, E.M. Khalifa, N.A. Sadik, S.Y. Abbas, A.G. Alsehemi, A.G. Ammar, Synthesis, characterization, and evaluation of some novel 4(3H)-quinazolinone derivatives as anti-inflammatory and analgesic agents, Med. Chem. Res. 22 (2013) 440 - 452.10.1007/s00044-012-0046-6
Search in Google Scholar Back to article
[11]. R.V. Coombs, R.P. Danna, M. Denzer, G.E. Hardtmann, B. Huegi, G. Koletar, J. Koletar, H. Ott, E. Jukniewicz, Synthesis and antiinflammatory activity of 1-alkyl-4-aryl-2(1H)-quinazolines and quinazolinethiones, J. Med.Chem. 16 (1973) 1237 - 1245.10.1021/jm00269a0064747965
Search in Google Scholar Back to article
[12]. R.S. Giri, H.M. Thaker, T. Giordano, J. Williams, D. Rogers, V. Sudersanam, K.K. Vasu, Design, synthesis and characterization of novel 2-(2, 4-disubstituted-thiazole-5-yl)-3-aryl-3H-quinazoline-4-one derivatives as inhibitors of NF-κB and AP-1 mediated transcription activation and as potential anti-inflammatory agents, Eur. J. Med. Chem. 44 (2009) 2184 - 2189.10.1016/j.ejmech.2008.10.03119064304
Search in Google Scholar Back to article
[13]. M.M. Gineinah, M.A. El-Sherbeny, M.N. Nasr, A.R. Maarouf, Synthesis of antiinflammatory screening of some quinazoline derivatives, Arch. Pharm. Pharm. Med. Chem. 11 (2002) 556 - 562.10.1002/ardp.20029000912596220
Search in Google Scholar Back to article
[14]. Q. Chao, L. Deng, H. Shih, L.M. Leoni, D. Genini, D.A. Carson, H.B. Cottam, Substituted isoquinolines and quinazolines as potential antiinflammatory agents. Synthesis and biological evaluation of inhibitors of tumor necrosis factor α, J. Med. Chem. 42 (1999) 3860 - 3873.10.1021/jm980590010508435
Search in Google Scholar Back to article
[15]. V. Alagarsamy, V. Muthukumar, M. Pavalarani, P. Vasanthanathan, R. Revathi, Synthesis, analgesic and anti-inflammatory activities of some novel 2,3-disubstituted quinazolin-4(3h)-ones, Biol. Pharm. Bull. 2003, 26, 557 - 559.10.1248/bpb.26.557
Search in Google Scholar Back to article
[16]. A.M. Alafeefy, A.A. Kadi, O.A. Al-Deeb, K.E. El-Tahir, N.A. Al-Jaber, Synthesis, analgesic and anti-inflammatory evaluation of some novel quinazoline derivatives, Eur. J. Med. Chem. 11 (2010) 4947 - 4952.10.1016/j.ejmech.2010.07.06720817329
Search in Google Scholar Back to article
[17]. S.M. Perez, M. Perez, A. Susunaga, M.A. Zavala, Anti-inflammatory activity of Lippia dulcis, J. Ethanopharmacol. 102 (2005) 1-4.10.1016/j.jep.2005.06.04716169695
Search in Google Scholar Back to article
[18]. J. Silva, W. Abebeb, S.M. Sousa, V.G. Duarte, M.I.L. Machadoc, F.J.A. Matos, Analgesic and anti-inflammatory effects of essential oils of eucalyptus, J. Ethanopharmacol. 89 (2003) 277-283.10.1016/j.jep.2003.09.00714611892
Search in Google Scholar Back to article

Design, synthesis and evaluation of anti-inflammatory, analgesic and antibacterial activity of 2, 4, 6-trisubstituted quinazoline derivatives

Abstract

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