: Monoamine oxidases inhibitors from Colvillea racemosa: Isolation, biological evaluation, and computational study

Research Abstract

Bioassay-guided fractionation and chemical investigation of Colvillea racemosastems led to identification of two new α, β-dihydroxydihydrochalcones, colveol A (1) and colveol B (2) along with fifteen known compounds. The structures were elucidated via interpretation of spectroscopic data. The absolute configurations of the dihydrochalcones 1 and 2 were assigned by a combination of chemical modification and electronic circular dichroism data. The isolated compounds were evaluated for their inhibition activity toward recombinant human monoamine oxidases (rhMAO-A and -B). Compound 1demonstrated preferential inhibition against hMAO-A isoenzyme (IC50 0.62 μM, SIA/B 0.02) while S-naringenin (13) and isoliquiritigein (15) demonstrated preferential hMAO-B inhibition (IC50 0.27 and 0.51 μM, SIA/B31.77 and 44.69, respectively). Fisetin (11) showed inhibition against hMAO-A with IC50 value of 4.62 μM and no inhibitory activity toward hMAO-B up to 100 μM. Molecular docking studies for the most active compounds were conducted to demonstrate the putative binding modes. It suggested that 1interacts with Gln215, Ala111, Phe352, and Phe208 amino acid residues which have a role in the orientation and stabilization of the inhibitor binding to hMAO-A, while S-naringenin (13) occupies both entrance and substrate cavities and interacts with Tyr326, a critical residue in inhibitor recognition in hMAO-B.

Research Keywords

monomine- colvillea