Design, synthesis, and biological evaluation of 2-(4-(methylsulfonyl) phenyl) indole derivatives with promising COX-2 inhibitory activity

Ahmed M. M. Shaker; Eman K. A. Abdelall; Khaled R. A. Abdellatifâ€Š; Hamdy M. Abdel-Rahman

doi:10.7324/JAPS.2018.81101

Abstract

A series of 2-(4-(methylsulfonyl)phenyl)-1-substituted-indole derivatives 4a–f was designed and synthesized as indomethacin analogs; All synthesized compounds were assessed for their in vitro COX-2 inhibition effect as well as in vivo anti-inflammatory activity using indomethacin as a reference drug. All synthesized compounds showed good anti-inflammatory activity and more selectivity for COX-2 inhibition. A molecular modeling study was carried out and the results were compatible with that derived from in vitro COX-2 inhibition assays.

Keyword: Indole indomethacin anti-inflammatory activity selective COX-2 molecular modeling.

Citation:

Shaker AMM, Abdelall EKA, Abdellatif KRA, AbdelRahman HM. Design, synthesis and biological evaluation of 2-(4-(methylsulfonyl)phenyl) indole derivatives with promising COX-2 inhibitory activity. J App Pharm Sci, 2018; 8(11): 001–008.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Reference

Abdelazeem AH, Abdelatef SA, El-Saadi MT, Omar HA, Khan SI, McCurdy CR, El-Moghazy SM. Novel pyrazolopyrimidine derivatives targeting COXs and iNOS enzymes: design, synthesis and biological evaluation as potential anti-inflammatory agents. Eur J Pharm Sci, 2014;62:197–211.

Abdellatif KR, Abdelgawad MA, Elshemy HA, Alsayed SS. Design, synthesis and biological screening of new 4-thiazolidinone derivatives with promising COX-2 selectivity, anti-inflammatory activity and gastric safety profile. Bioorg Med Chem, 2016a; 64:1–12.

Abdellatif KR, Lamie PF, Omar HA. 3-Methyl-2-phenyl-1- substituted-indole derivatives as indomethacin analogs: design, synthesis and biological evaluation as potential anti-inflammatory and analgesic agents. J Enzyme Inhib Med Chem, 2016b;31:318–24.

Bandgar BP, Sarangdhar RJ, Viswakarma S, Ahamed FA. Synthesis and biological evaluation of orally active prodrugs of indomethacin. J Med Chem, 2011; 54:1191–201.

Brune K, Patrignani P. New insights into the use of currently available non-steroidal anti-inflammatory drugs. J Pain Res, 2015; 8:105.

Bruno A, Tacconelli S, Patrignani P. Variability in the response to non-steroidal anti-inflammatory drugs: mechanisms and perspectives. Basic Clin Pharmacol Toxicol, 2014; 114:56–63.

Chowdhury MA, Huang Z, Abdellatif KR, Dong Y, Yu G, Velázquez CA, Knaus EE. Synthesis and biological evaluation of indomethacin analogs possessing a N-difluoromethyl-1, 2-dihydropyrid-2-one ring system:a search for novel cyclooxygenase and lipoxygenase inhibitors. Bioorg Med Chem Lett, 2010; 20:5776–80.

Di Fiore A, Pedone C, D’Ambrosio K, Scozzafava A, De Simone G, Supuran CT. Carbonic anhydrase inhibitors: valdecoxib binds to a different active site region of the human isoform II as compared to the structurally related cyclooxygenase II ‘selective’ inhibitor celecoxib. Bioorg Med Chem Lett, 2006; 16:437–42.

Harirforoosh S, Asghar W, Jamali F. Adverse effects of nonsteroidal antiinflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Res, 2014; 16:821–47.

Jutti Levita AN, Mutholib A, Ibrahim S. Andrographolide inhibits COX-2 expression in human fibroblast cells due to its interaction with arginine and histidine in cyclooxygenase site. J J Appl Sci, 2010;10:1481–4.

Kaur J, Bhardwaj A, Huang Z, Knaus EE. N-1 and C-3 substituted indole Schiff bases as selective COX-2 inhibitors: synthesis and biological evaluation. Bioorg Med Chem Lett, 2012; 22:2154–9.

Kirkby NS, Chan MV, Zaiss AK, Garcia-Vaz E, Jiao J, Berglund LM, Verdu EF, Ahmetaj-Shala B, Wallace JL, Herschman HR, Gomez MF. Systematic study of constitutive cyclooxygenase-2 expression: role of NF-κB and NFAT transcriptional pathways. Proc Natl Acad Sci, 2016; 113:434–9.

Lakshman TR, Deb J, Paine TK. Anti-inflammatory activity and enhanced COX-2 selectivity of nitric oxide-donating zinc (ii)–NSAID complexes. Dalton Trans, 2016; 45:14053–7.

Pathak RK, Marrache S, Choi JH, Berding TB, Dhar S. The prodrug platin-A: simultaneous release of cisplatin and aspirin. Angew Chem Int Ed, 2014; 53:1963–7.

Pountos I, Georgouli T, Calori GM, Giannoudis PV. Do nonsteroidal anti-inflammatory drugs affect bone healing? A critical analysis. Sci World J, 2012; 2012:14.

Raju D, Basavaraju Y. Synthesis of new tetralone ester intermediates for podophyllotoxin analogues. Pure Appl Chem, 2013; 1:43–9.

Regulski M, Regulska K, PrukaÅ‚a W, Piotrowska H, Stanisz B, Murias M. COX-2 inhibitors: a novel strategy in the management of breast cancer. Drug Discov Today, 2016; 21:598–615.

Sostres C, Gargallo CJ, Lanas A. Nonsteroidal anti-inflammatory drugs and upper and lower gastrointestinal mucosal damage. Arthritis Res Ther, 2013; 15:S3.

Van Breemen RB, Tao Y, Li W. Cyclooxygenase-2 inhibitors in ginger (Zingiber officinale). Fitoterapia, 2011; 82:38–43.

Wehling M. Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol, 2014; 70:1159–72.

Yu B, Liu A-H, He L-N, Li B, Diao Z-F, Li Y-N. Catalyst-free approach for solvent-dependent selective oxidation of organic sulfides with oxone. Green Chem, 2012; 14:957–62.

Zarghi A, Tahghighi A, Soleimani Z, Daraie B, Dadrass OG, Hedayati M. Design and synthesis of some 5-substituted-2-(4-(azido or methylsulfonyl) phenyl)-1H-indole derivatives as selective cyclooxygenase (COX-2) inhibitors. Sci Pharm, 2008; 76:361–76.

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