Antioxidant, cytotoxicity, and QSAR study of 1-adamantylthio derivatives of 3-picoline and phenylpyridines

Abstract

A series of isomeric α- and β-(1-adamantylthio)pyridines were previously documented to possess interesting antimicrobial and antimalarial activities. In this study, the antioxidant and cytotoxic potentials of 1-adamantylthio-3-methyl and 2-,3-,4-phenylpyridines (1–10) were investigated. The tested compounds were shown to exhibit interesting superoxide (SOD)- and free radical (DPPH)-scavenging activities as well as cytotoxic activities. Particularly, β-(1-adamantylthio)-4-phenylpyridine (8) was shown to be the most potent antioxidant and cytotoxic compound. QSAR studies revealed that dipole moment (μ) and electrophilic index (ωi) were the most important descriptors accounting for the observed SOD activities. Compounds with high μ and ωi values were observed to display high SOD activity. Inversely, compounds with the lowest atomic polarizability (MATS4p) exhibited the highest DPPH activity. Other quantum chemical descriptors such as atomic masses (GATS4m), ωi, and LUMO energy were also well correlated with cytotoxicity. The findings demonstrated that thiopyridine 8 is a potential lead compound that should be further investigated in drug discovery efforts. The QSAR results offer good prospect for the rational design of novel compounds with robust bioactivities.