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Abstract

DESIGN, SYNTHESIS AND EVALUATION OF SUBSTITUTED COUMARIN DERIVATIVES AS NEW SCAFFOLD ON PARKINSON’S DISEASE

Siju E. N.*, Vishnupriya C. P., Saranya Balan, Hariraj N., Rahul K., Vivek D., Aiswarya Lakshmi A. G., Minil M. and Bijesh Vatakeel

Abstract

Coumarins are naturally occurring heterocyclic compounds with multifactorial medicinal properties. The strategy of the present study is design,synthesis, and evaluation of certain substituted coumarin derivatives as a new scaffold on Parkinson’s disease(PD).A series of substituted coumarin derivatives were designed and molecular modeling studies of these compounds were carried out using the docking program Argus lab 4.0.1 version. MAO(monoamine oxidase) inhibitory activity of the compound was assessed by sensitive quantitative colorimetric assay which gives an account on monoamine oxidase activity. Then, in vivo pharmacological studies carried out by the evaluation of hind limb rigidity using the model reserpine antagonism in rats. All results were compared statistically by one way ANOVA using Graph Pad Prism.Molecular modeling studies revealed that the compound H2D was able to bind simultaneously to amino acids in the activesite of the MAO enzyme. In MAO inhibition assay, the synthesized compound was evaluated as MAO-A and B inhibitors showing MAO inhibitory activities in micromolar range ((human)hMAO-A IC50 =3.70, hMAO-B IC50=3.9). And the result obtained from DPPH(1,1-diphenyl-2-picryl hydrazyl) assay showed that the compound exhibits a good antioxidant activity. In the evaluation of hind limb rigidity, compound H2D pretreated groups showed a significant reduction in rigidity when compared with the reserpine treated group. Among the designed series of substituted coumarin derivatives, compound H2D showedgood antioxidant property and MAO inhibitory activity. Based on these properties the synthesized compound H2D can be considered as a new scaffold on PD.

Keywords: MAO Inhibition, Coumarin derivatives, Parkinson’s disease.


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