Anti-cancer activity of 2,4-disubstituted thiophene derivatives: dual inhibitors of lipoxygenase and cyclooxygenase

Rakesh, K. S. and Jagadish, S. and Swaroop, T. R. and Mohan, C. D. and Ashwini, N. and Harsha, K. B. and Zameer, F. and Girish, K. S. and Rangappa, K. S. (2015) Anti-cancer activity of 2,4-disubstituted thiophene derivatives: dual inhibitors of lipoxygenase and cyclooxygenase. MEDICINAL CHEMISTRY, 11 (5). pp. 462-472. ISSN 1875-6638

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Official URL: http://doi.org/10.2174/1573406411666141210141918

Abstract

2,4-Disubstituted thiophene derivatives were synthesized and assessed for anti-inflammatory and anti-cancer activities by targeting two important enzymes of the arachidonic acid metabolism. Both lipoxygenase and cyclooxygenase enzymes play vital role in chronic inflammation and carcinogenesis. Previous studies have proved that COX-2 and 5-LOX are highly activated in various types of cancers; hence inhibition of these clinically important enzymes constitutes the essential criterion for the suppression of tumor progression and metastasis. Among the tested derivatives, 2d and 2g compounds emerged as potent inhibitors of lipoxygenase and cyclooxygenase enzymes. The potent inhibitor of cyclooxygenase was further tested for in vitro cytotoxicity on cervical cancer (HeLa) cells and in vivo tumor model studies using EAT bearing mice where 2-(3,4,5-trimethoxyphenyl)-4-(N-methylindol-3-yl) thiophene (2g) showed eloquent activity. Further, in silico modeling results confirmed the active catalytic ligand binding pockets, which is evident from higher atomic contact energy values of 2d and 2g than compared to standard drug. Thus, 2g may find better application in management of inflammation and in proapoptotic therapeutic engineering.

Item Type: Article
Subjects: C Chemical Science > Biochemistry
C Chemical Science > Chemistry
Divisions: Department of > Biochemistry
Department of > Chemistry
Depositing User: Shrirekha N
Date Deposited: 18 Jun 2019 10:13
Last Modified: 18 Jun 2019 10:13
URI: http://eprints.uni-mysore.ac.in/id/eprint/3255

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