Abstract

A series of new 6-amidocoumarin derivatives, 3a–j, was synthesized and evaluated for their inhibitory activity against monoamine oxidase (MAO) and cholinesterase. All compounds, except 3 g, showed higher inhibitory activity towards MAO-B than MAO-A. Compound 3i most potently inhibited MAO-B with an IC50 value of 0.095 μM, followed by 3j (0.150 μM), 3b (0.190 μM), and 3c (0.204 μM). Compound 3i demonstrated the highest selectivity index (>421.05) for MAO-B. The remarkable MAO-B inhibitory activity of compounds 3i, 3j, 3b, and 3c highlighted the substantial role of the substituents at the 3,4-position of the terminal phenyl group in achieving optimal MAO-B inhibition, especially 3-Cl (3i) > 3-CF3 (3b). In the kinetic study, the Ki value of 3i for MAO-B was 0.046 ± 0.010 μM with a competitive reversible mode. Moreover, compounds 3i and 3j were nontoxic to normal (MDCK), cancer (HL-60), and neuroblastoma (SH-SY5Y) cells and showed protective effects against damage induced by reactive oxygen species in SH-SY5Y neuroblastoma cells. Moreover, molecular docking and molecular dynamics simulations highlighted the tight interactions of 3i with Tyr398 at the binding site of MAO-B. These findings suggest that 3i is a potent, reversible, and selective MAO-B inhibitor that could potentially treat neurological disorders.

Full Text
Paper version not known

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.