Theoretical Study of Correlation Between Substituent Effect in Synthetic Cathinones and Their Cytotoxic Activity

Cathinone and its synthetic derivatives are among the most popular classes of narcotics worldwide. Experimental studies have demonstrated variable cytotoxic activity among these substances. Until now, the research on cathinones has been limited to their psychotropic activity. Therefore, the structure–activity correlation in this group remains poorly understood. The current study aimed to expand the understanding of the influence of cathinone structural modifications on cytotoxic activity. A group of cathinones whose cytotoxic activity has been experimentally analyzed by a single research group was studied in silico using density functional theory (DFT). A systematic characterization of the substituent effect and the aromaticity changes depending on the polarity of the medium is presented in this paper. A correlation between growing electron-withdrawing properties of the N-end and its carbonyl fragment as well as aromaticity decrease with growing cytotoxic activity were observed.