Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study

0465178 - ÚEB 2017 RIV FR eng J - Journal Article
Lamie, P.F. - Ali, W.A.M. - Bazgier, Václav - Rárová, Lucie
Novel N-substituted indole Schiff bases as dual inhibitors of cyclooxygenase-2 and 5-lipoxygenase enzymes: Synthesis, biological activities in vitro and docking study.
European Journal of Medicinal Chemistry. Roč. 123, NOV 10 (2016), s. 803-813. ISSN 0223-5234. E-ISSN 1768-3254
R&D Projects: GA MŠMT(CZ) LO1204
Institutional support: RVO:61389030
Keywords : Indole derivatives * Antiproliferative activity * Anti-inflammatory activity
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 4.519, year: 2016

Two new series of N-substituted indole derivatives 4a-1 and 5a-h were synthesized. Their chemical structures were confirmed using spectroscopic tools including IR, H-1 NMR,C-13 NMR mass spectroscopy and elemental analyses. The results showed no significant cytotoxic activity on either cancer or normal human cells. Anti-inflammatory activity for all target compounds was evaluated in vitro. Compounds 5a -h were found to have better anti-inflammatory activity than 4a-1. The inhibitory activity of COX-2 and 5-LOX were tested for 5a-h. Three compounds, 5c, 5d and 5f showed excellent COX-2 inhibitory activity with IC50 ranging from 0.98 to 1.23 mu M compared to the reference celecoxib (1.54 mu M). These compounds had a reasonable selectivity index between 7.03 and 8.05. Additionally, p-methylbenzoyl derivative 5g (IC50 = 5.78 M) had superior 5-LOX inhibitory activity, higher than quercetin. 5e was close to quercetin in its LOX inhibitory activity. Compounds 5a h were docked inside the active site of COX-2 and 5-LOX enzymes.
Permanent Link: http://hdl.handle.net/11104/0263843