Natural based piperine derivatives as potent monoamine oxidase inhibitors: an in silico ADMET analysis and molecular docking studies

• Published in: BMC chemistry Vol. 14; no. 1; p. 12
• Main Authors: Dhiman, Priyanka, Malik, Neelam, Khatkar, Anurag
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 17-02-2020; Springer Nature B.V; BMC
• Subjects: Antioxidants; Chemical compounds; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Derivatives; DPPH; Free radicals; H2O2 activity; Hydrogen peroxide; In silico design; Inhibitors; Mathematical analysis; Medicinal Chemistry; Molecular docking; Monoamine oxidase; Oxidase; Pharmacology; Piperine derivatives; Research Article; Scavenging; Monoamine oxidase; In silico design; DPPH; activity; Piperine derivatives; H; O; H2O2 activity
• ISSN: 2661-801X; 2661-801X
• DOI: 10.1186/s13065-020-0661-0

Neurodegenerative disorders follow numerous pathological ways concerning overexpression of monoamine oxidase and formation of reactive oxygen species. The computational design of the piperine derivatives has given the significant MAO inhibitors with considerable antioxidant potential. Molecular docking provided the mechanistic insight of the compounds within the hMAO active site. In the current study we have prepared a series of compounds related to piperine and investigated them through monoamine oxidase A and B assay and evaluated the free radical scavenging activity. The synthesized compounds were analyzed by using in silico techniques within the active site of MAO and the ADMET properties were also calculated. The results obtained in this study indicated the interesting therapeutic potential of some compounds such as
7
and
17c
as most promising hMAO-A inhibitors whereas compounds
15
,
5
and
17b
were found as hMAO-B inhibitors. Moreover, we assessed the antioxidant potential of the piperine analogues and compounds
5
,
17b
, and
7
showed very modest antioxidant activity against DPPH and H
2
O
2
radicals. The outcome of the study indicating that the piperine related derivatives are found as considerable MAO inhibitors and antioxidants. Moreover, the SAR structure activity relationships are depicting the structural features required for the MAO inhibition. In case of MAO activity, good correlations were found among the calculated and experimental results.