Two dimensional-QSAR and molecular dynamics studies of a selected class of aldoxime- and hydroxy-functionalized chalcones as monoamine oxidase-B inhibitors

Abstract

Candidates generated from unsaturated ketone (chalcone) demonstrated as strong, reversible and specific monoamine oxidase-B (MAO-B) inhibitory activity. For the research on MAO-B inhibition, our team has synthesized and evaluated a panel of aldoxime-chalcone ethers (ACE) and hydroxylchalcones (HC). The MAO-B inhibitory activity of several candidates is in the micro- to nanomolar range in these series. The purpose of this research was to develop predictive QSAR models and look into the relation between MAO-B inhibition by aldoxime and hydroxyl-functionalized chalcones. It was shown that the molecular descriptors ETA Shape P, MDEO-12, ETA dBetaP, SpMax1 Bhi and ETA EtaP B are significant in the inhibitory action of the MAO-B target. Using the current 2D QSAR models, potential chalcone-based MAO-B inhibitors might be created. The lead molecules were further analyzed by the detailed molecular dynamics study to establish the stability of the ligand–enzyme complex.

Communicated by Ramaswamy H. Sarma

Keywords:

• 2D-QSAR
• monoamine oxidase-B
• chalcones
• molecular dynamics

Acknowledgments

The authors are thankful to PaDEL developers for providing the free versions of their software and to Dr. Paola Gramatica, Italy and her team for providing QSARINS-2.2 (www.qsar.it).

Disclosure Statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This research was supported by a grant from the Amrita Vishwa Vidyapeetham University (Seed Grant Number K‐PHAR‐20‐628 to B. Mathew).