Title:Exploration of Umbelliferone Based Derivatives as Potent MAO Inhibitors: Dry vs. Wet Lab Evaluation
VOLUME: 18 ISSUE: 21
Author(s):Priyanka Dhiman, Neelam Malik and Anurag Khatkar*
Affiliation:Faculty of Pharmaceutical Sciences, M.D. University, Rohtak (124001), Haryana, Faculty of Pharmaceutical Sciences, M.D. University, Rohtak (124001), Haryana, Faculty of Pharmaceutical Sciences, M.D. University, Rohtak (124001), Haryana
Keywords:Neuropsychological implications, Neurodegenerative disorders, Monoamine oxidase, In silico drug design, Umbelliferone
derivatives, Oxidative stress, Radical scavenging action.
Abstract:Background: Monoamine oxidase inhibitors are potential drug candidates within therapeutics
of different neuropsychological and neurodegenerative disorders including anxiety, depression and Parkinson’s
disease.
Objective: We investigated the MAO inhibitory effects of the umbelliferone based derivatives for the
treatment of neurological disorders. The potential antioxidant effects of the derivatives were evaluated
by DPPH and H2O2 scavenging methods.
Method: A series of different umbelliferone derivatives was designed and synthesized, and the derivatives
were screened for hMAO-A and hMAO-B inhibition. Moreover, the mechanistic insight for enzyme-
compound infractions was achieved by docking simulation. The antioxidant potential was dually
assessed by two spectrophotometric titrations methods.
Results: Compound 5 with bromo 5-bromo-isatin exhibited a remarkable hMAO-A inhibitory potential
(7.473±0.035 µM and the selectivity index of 0.14) revealing the impact of hybrid coumarin and 5-
bromo-2-oxoindolin-3-yl ring with hydrazine linker on the hMAO-A active site. Compound 13 exhibited
significant hMAO-B inhibition with an IC50 value of 10.32±0.044µM with an exceptional selectivity
index of 8.55. Incorporation of 2-hydroxy-2-phenylacetate moiety on 2-oxo-2H-chromen ring led
the important binding infractions within the hMAO active site.
Conclusion: Our findings revealed a good correlation between experimental MAO inhibition and docking
score by computational studies. Notably, the compounds with remarkable MAO inhibitory potential
were also observed as potential antioxidants.
