Synthesis of 1,3,4-Thiadiazole Derivatives and Their Anticancer Evaluation

Abstract

Thiadiazole derivatives have garnered significant attention in the field of medicinal chemistry due to their diverse pharmacological activities, including anticancer properties. This article presents the synthesis of a series of thiadiazole derivatives and investigates their chemical characterization and potential anticancer effects on various cell lines. The results of the nuclear magnetic resonance (NMR) analyses confirmed the successful formation of the target compounds. The anticancer potential was evaluated through in silico and in vitro cell-based assays using LoVo and MCF-7 cancer lines. The assays included cell viability, proliferation, apoptosis, and cell cycle analysis to assess the compounds’ effects on cancer cell growth and survival. Daphnia magna was used as an invertebrate model for the toxicity evaluation of the compounds. The results revealed promising anticancer activity for several of the synthesized derivatives, suggesting their potential as lead compounds for further drug development. The novel compound 2g, 5-[2-(benzenesulfonylmethyl)phenyl]-1,3,4-thiadiazol-2-amine, demonstrated good anti-proliferative effects, exhibiting an IC50 value of 2.44 µM against LoVo and 23.29 µM against MCF-7 after a 48-h incubation and little toxic effects in the Daphnia test.

Techniques and Strategies in Drug Design and Discovery

“…Mechanistic studies in cell lines and activity observed in a mouse xenograft model in vivo are also detailed. Stecoza et al [14] used a similar scaffold-based technique to develop new 1,3,4-thiadiazol-2-amine derivatives as anti-proliferative agents. The use of in silico methods like the PASS (Prediction of Activity Spectra for Substances) application [15,16] and docking studies indicated STAT3, Mcl-1, and CDK9 as the most likely mechanisms responsible for the anti-cancer effects.…”