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

Publication Type : Journal Article

Publisher : Arch Pharm (Weinheim)

Source : Arch Pharm (Weinheim), Volume 349, Issue 8, p.627-37 (2016)

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Keywords : Antioxidants, Binding Sites, blood-brain barrier, Chalcones, Hep G2 Cells, Humans, Indoles, Inhibitory Concentration 50, kinetics, Molecular Docking Simulation, Monoamine oxidase, Monoamine Oxidase Inhibitors, Structure-Activity Relationship

Campus : Kochi

School : School of Pharmacy

Department : Pharmaceutical Chemistry & Analysis

Year : 2016

Abstract : 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.

Cite this Research Publication : R. Sasidharan, Manju, S. Leelabaiam, Ucar, G., Baysal, I., and Bijo Mathew, “Identification of Indole-Based Chalcones: Discovery of a Potent, Selective, and Reversible Class of MAO-B Inhibitors.”, Arch Pharm (Weinheim), vol. 349, no. 8, pp. 627-37, 2016.

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