Identification of Indole ‐Based Chalcones: Discovery of a Potent, Selective, and Reversible Class of MAO‐B Inhibitors

A series of 11 indole‐based chalcones (IC1–11) with various electron donating and withdrawing groups at the para position of the phenyl ring B were synthesized. All the compounds were tested for their human monoamine oxidase (hMAO)‐A and hMAO‐B inhibitory potencies. Most of the synthesized candidates proved to be potent and selective inhibitors of MAO‐B rather than MAO‐A, with a reversible and competitive mode. Among them, compound IC9 was found to be a potent inhibitor of hMAO‐B with Ki = 0.01 ± 0.005 μM and a selectivity index of 120. It was found to be better than the standard drug, selegiline (hMAO‐B with Ki = 0.20 ± 0.020 μM) with a selectivity index of 30.55. PAMPA assays were carried out for all the compounds in order to evaluate the capacity of the compounds to cross the blood–brain barrier. Moreover, the most potent MAO‐B inhibitor, IC9, was nontoxic at 5 and 25 μM, with 95.20 and 69.17% viable cells, respectively. The lead compound IC9 has an antioxidant property of 1.18 Trolox equivalents by ABTS assay. Molecular modeling studies were performed against hMAO‐B to observe binding site interactions of the lead compound. Eleven indole‐based chalcones with various electron donating and withdrawing groups at the para position of the phenyl ring B were synthesized and tested for their human monoamine oxidase (hMAO)‐A and hMAO‐B inhibitory potencies. IC9 was the most potent inhibitor of hMAO‐B with Ki = 0.01 ...
Source: Archiv der Pharmazie - Category: Drugs & Pharmacology Authors: Tags: Full Paper Source Type: research