A Computational Study of Cytotoxicity of Substituted Amides of Pyrazine-2-carboxylic acids Using QSAR and DFT Based Molecular Surface Electrostatic Potential

Abstract

Pyrazine derivatives are important class of compounds with diverse biological and cytotoxic activities and clinical applications. In this study, B3 p 86 / 6 – 31 + + G * was used to compute and map the molecular surface electrostatic potentials of a group of substituted amides of pyrazine-2-carboxylic acids to identify common features related to their subsequent cytotoxicities. Several statistical properties including potentials extrema (Vs ,min,Vs ,max), the average of positive electrostatic potential on the surface (Vs+), the average of V(r) over the surface (Vs) and the Lowest Unoccupied Molecular Orbital (LUMO) and system cytotoxicities were computed. Statistically, the most significant correlation is a five -parameter equation with correlation coefficient, R² values of 0.922 and R²adj = 0.879. The obtained models allowed us to reveal cytotoxic activity of substituted amides of Pyrazine2- carboxcylic acid.