Virtual Screening of Alkaloids and Flavonoids as Acetylcholinesterase and MAO-B Inhibitors by Molecular Docking and Dynamic Simulation Studies

Abstract

The neuroprotective actions of flavonoids and alkaloids have been reported in many cognitive disorders. The study was focused on twenty-four phytoconstituents (alkaloids and flavonoids) to screen their activity against neurodegenerative diseases. The molecular interactions were analyzed between the phytoconstituents and the acetylcholinesterase and monoamine oxidase-B enzymes by computational studies such as molecular docking, binding free energy determination, molecular dynamics, pharmacophore modeling, and ADMET. The well-interacted compounds were piperine and rutin, which has high inhibitory potential than the enzymes' co-crystals. Molecular dynamics confirmed the stability of piperine-2V60 and rutin-6O4W complexes, and pharmacophore modeling studies confirmed the hydrogen bonding interactions. Physicochemical and ADMET properties were carried out, highlighting the druglikeness and oral bioavailability of the compounds. PASS online tool predicted the phytoconstituents biological spectrum against the enzyme involved in neurodegenerative diseases. Further, these compounds should be pharmacologically explored to develop as good leads for treating neurodegenerative diseases.

Keywords:

• Alkaloids
• flavonoids
• molecular docking
• molecular dynamics
• pharmacophore modeling
• ADMET

Acknowledgements

We acknowledge NITTE Deemed to be University, NGSM Institute of Pharmaceutical Sciences, Mangaluru, Karnataka, for providing the financial support and NGSMIPS CADD Lab, Mangaluru, Karnataka for the facilities to perform this work.

Disclosure statement

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