Two new series of N-substituted indole derivatives 4a-l and 5a-h were synthesized. Their chemical structures were confirmed using spectroscopic tools including IR, (1)H NMR, (13)C 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-l. 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 μM compared to the reference celecoxib (1.54 μM). These compounds had a reasonable selectivity index between 7.03 and 8.05. Additionally, p-methylbenzoyl derivative 5g (IC50 = 5.78 μM) 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.
- MeSH
- antiflogistika chemická syntéza chemie metabolismus farmakologie MeSH
- arachidonát-5-lipoxygenasa chemie metabolismus MeSH
- cyklooxygenasa 1 metabolismus MeSH
- cyklooxygenasa 2 metabolismus MeSH
- indoly chemická syntéza chemie metabolismus farmakologie MeSH
- inhibitory cyklooxygenasy 2 chemická syntéza chemie metabolismus farmakologie MeSH
- inhibitory lipoxygenas chemická syntéza chemie metabolismus farmakologie MeSH
- katalytická doména MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- protinádorové látky chemická syntéza chemie metabolismus farmakologie MeSH
- racionální návrh léčiv * MeSH
- Schiffovy báze chemie MeSH
- simulace molekulového dockingu * MeSH
- techniky syntetické chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
