QSAR studies on indole-azole Analogues using DTC tools; imidazole ring is more favorable for aromatase inhibition

Abstract

Abstract Quantitative structure activity relationship (QSAR) studies have been performed on indole-azole based compounds to correlate molecular descriptors and aromatase inhibitory activity using Drug Theoretics and Cheminformatics (DTC) tools. For 2- and 3- [(aryl) (azolyl)methyl]indole derivatives (set-I), MATS4s, AATS4e, and ATSC7i showed good correlation with significant R2 and Q2 values as 0.93 and 0.83, while for 1-aryl-2-[(1H-imidazol-1-yl)methyl]-6-substituted-1H-indole derivatives (set-II), the derived QSAR model showed significant R2 and Q2 values as 0.93 and 0.82 respectively, with the descriptors AVP-0, MATS7s, minHaaCH. Electronic parameters such as high electronegativity and ionization potential have unfavourable influence on anti-aromatase activity of both series of compounds. Among the imidazole and 1, 2, 4-triazole rings, imidazole nucleus is more favourable due to its low electrostatic potential. The findings of the study might guide in future designing and development of more potent indole-azole based aromatase inhibitors.