COMFA Analysis and toxicity risk assessment of coumarin analogues as Mao-A Inhibitors: Attempting better insight in drug design

By Rahul D. Jawarkar, Devidas T.  Mahajan, Vijay H. Masand, Taibi Ben Hadda, G. H. Kurhade

ABSTRACT


Monoamine Oxidase (MAO) plays vital role in regulation of monoamine neurotransmitters such as serotonin, dopamine and nor-adrenaline. MAO inhibitors are used in the treatment of Parkinson’s disease, Alzheimer’s disease, depression etc. In present work we have carried out Comparative Molecular Field Analysis to understand the pharmacological activities of Coumarin Analogues as MAO-A inhibitors. The 3D QSAR analysis provides interesting insights in understanding the Steric and Electronic structural requirements for MAO-A inhibitory activity. The energy minimized conformations were obtained by molecular mechanics using SYBYL package. The developed model with r2 value of 0.79 and Predictive r2 value of = 0.730 for MAO-A Inhibitors. The respective relative contributions of steric and electrostatic fields were 46.7 and 53.3 %, indicating that Electrostatic field is more predominant. Further all molecules were subjected to the toxicity risk assessment using Molinspiration and Osiris Calculations. Among the various MAO-A inhibitors, compound no-3 and compound no-12 are optimum drug candidate with respect to the activity and toxicity.

Keywords: MAO, COMFA, steric, electrostatic, Molinspiration, Osiris.

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