DFT-QSAR and Molecular Docking Studies on 1,2,3-Triazole-Dithiocarbamate Hybrids as Potential Anticancer Agents

Recently, considerable attention has been drawn on the search for novel anticancer drugs in order to improve survival rates and wellbeing of cancer patients. 1,2,3-triazole is an attractive scaffold possessing diverse biological activities. The quantitative structure–activity relationship (QSAR) is a powerful computational tool which has widened the scope of rational drug design, as well as the search for the mechanisms of drug actions. A series of novel 1,2,3-triazole-dithiocarbamate hybrids (1,2,3-TDHs) were studied for anticancer activity against human gastric cancer cell line (MGC-803) using Density Functional Theory (DFT), Quantitative Structure Activity Relation (QSAR) and Docking approaches. QSAR models were successfully constructed with acceptable predictive performance. The QSAR analysis indicated that certain molecular descriptors namely EHOMO, ELUMO, Log P, Area, the total electronic charges on the heteroatom (H), and the average electronic charge on the heteroatoms (H_HET4r) are important factors for the observed biological activity. The results from docking study predicted stable conformations of the ligands within the enzyme’s active gouge of the receptor. Compound E, tert Butyl 4-(((1-(4-methylbenzyl)-1H-1,2,3-triazol-4-yl)methylthio)carbonothioyl)-piperazine-1-arboxylate, formed the most stable complex with the protein receptor.