Novel class of benzimidazole-thiazole hybrids: The privileged scaffolds of potent anti-inflammatory activity with dual inhibition of cyclooxygenase and 15-lipoxygenase enzymes.

Bioorganic & Medicinal Chemistry
Mohammed T-E MaghrabyOla I A Salem

Abstract

The present study includes design and synthesis of new molecular hybrids of 2-methylthiobenzimidazole linked to various anti-inflammatory pharmacophores through 2-aminothiazole linker, to investigate the effect of such molecular variation on cyclooxygenase (COX) and 15-lipoxygenase (15-LOX) enzymes inhibition as well as in vivo anti-inflammatory activity. The chemical structures of new hybrids were confirmed using different spectroscopic tools and elemental analyses. Benzimidazole-thiazole hybrids linked to acetyl moiety 13, phenyl thiosemicarbazone 14, 1,3-thiazolines 15a-c and 4-thiazolidinone 16 exhibited significant COX-2 inhibition (IC50 = 0.045-0.075 µM) with significant COX-2 selectivity indices (SI = 142-294). All hybrids revealed potent 15-LOX inhibitory activity (IC50 = 1.67-6.56 µM). Benzimidazole-thiazole hybrid 15b was the most potent dual COX-2 (IC50 = 0.045 µM, SI = 294) inhibitor approximate to celecoxib (COX-2; IC50 = 0.045 µM, SI = 327), with double inhibitory activity versus 15-LOX enzyme (IC50 = 1.67 µM) relative to quercetin (IC50 = 3.34 µM). Three hybrids (14, 15b &16) were selected for in vivo screening using carrageenan-induced paw edema method. Benzimidazole-thiazole hybrid linked to 4-thiazolidinone 16...Continue Reading

References

Dec 1, 1962·Proceedings of the Society for Experimental Biology and Medicine·C A WINTERG W NUSS
Jan 7, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marc Peters-GoldenMichael J Coffey
Feb 11, 2009·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Praveen Rao, Edward E Knaus
May 28, 2009·Journal of Enzyme Inhibition and Medicinal Chemistry·Ritesh N SharmaShyam S Pancholi
Mar 23, 2010·Cell·Ruslan Medzhitov
Mar 23, 2010·Cell·Sergei I GrivennikovMichael Karin
Apr 22, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Emanuela Ricciotti, Garret A FitzGerald
Sep 23, 2011·Chemical Reviews·Jesper Z Haeggström, Colin D Funk
Jul 4, 2012·Bioorganic & Medicinal Chemistry Letters·Finn K HansenDetlef Geffken
Oct 4, 2012·Bioorganic & Medicinal Chemistry·Yogita Bansal, Om Silakari
Jan 8, 2014·Journal of Pharmacy & Pharmaceutical Sciences : a Publication of the Canadian Society for Pharmaceutical Sciences, Société Canadienne Des Sciences Pharmaceutiques·Sam HarirforooshFakhreddin Jamali
Mar 8, 2014·European Journal of Medicinal Chemistry·Monika GabaChander Mohan
Aug 20, 2014·Medicinal Chemistry·Ankita RathoreMohammad Shahar Yar
Nov 3, 2015·Journal of Clinical Gastroenterology·James M Scheiman
Nov 19, 2015·Acta Pharmaceutica Sinica. B·Monika GabaChander Mohan
Apr 11, 2017·Future Medicinal Chemistry·Hassanein H HassaneinMona F Said
Feb 23, 2018·Oncotarget·Linlin ChenLing Zhao
Mar 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Konstantinos LiarasAthina Geronikaki

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Citations

Nov 3, 2020·Drug Development Research·Parteek Prasher, Mousmee Sharma
Oct 20, 2020·European Journal of Medicinal Chemistry·Begüm Nurpelin SağlıkZafer Asım Kaplancıklı
Apr 4, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Mohamed Farouk ElsadekMohamed Fawzi Farahat
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Aya C TakiRobin B Gasser
Jun 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Islam H El AzabNadia A A Elkanzi
Oct 12, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Ming BianGong Guo-Hua
Oct 16, 2021·Chemical Biology & Drug Design·Mar'iyah Najihah AbdullahShafida Abd Hamid

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