Refining the Structural Features of Chromones as Selective MAO‐B Inhibitors: Exploration of Combined Pharmacophore‐Based 3D‐QSAR and Quantum Chemical Studies

Synthetic chromones are considered as a validated target of the inhibition of monoamine oxidase‐B and its relationship to various neurodegenerative diseases is increasing. Herein described is pharmacophore generation and atom‐based 3D‐QSAR analysis of previously reported chromone based MAO−B inhibitors in order to get insight into their structural requirements responsible for high affinity. The best four‐point pharmacophore model with five features AAHRR‐3, two hydrogen bond acceptor (A),one hydrophobic groups (H) and two aromatic rings (R) as pharmacophore features was developed by PHASE module of Schrodinger suite. The pharmacophore hypothesis yielded a statistically significant 3D‐QSAR model, with a good correlation coefficient (R 2 =0. 8828), cross validation coefficient (Q 2 = 0. 7036), and F value 50.2. In this series, the potent molecule 6‐(3‐bromobenzyl)‐4 H ‐chromen‐4‐one ( 5 ) is further exploited for electrostatic potential surface and analyze the natural bond orbital toward the binding characteristics by using density functional theory calculations.