SYNTHESIS, CHARACTERIZATION, AND PHARMACEUTICAL ACTIVITY OF FUSED TRIAZOLOTHIADIAZOLE DERIVATIVES

Abstract: A series of fused heterocyclic compound Triazolothiadiazole Derivatives 4a-4f was produced by treating 4-amino-5-phenyl-4H-1,2,4-triazole-3-thiol (3) with aryl aldehydes in the presence of KOH. The new triazolothiadiazole derivatives demonstrated anticancer efficacy through docking with the EGFR tyrosine kinase receptor protein, evidenced by docking scores ranging from (-3.23) to (-3.99) kcal/mol in comparison to the control Xalkori’s value of (-3.22) kcal/mol. The new compounds were assessed for their vitro cytotoxic activities and tested against the MCF-7 cell line. The synthesized compounds exhibited significant cytotoxic action against the MCF-7 cell line while demonstrating no cytotoxicity toward the normal HdFnd cell line. Compared to normal cells, the study revealed a considerable selectivity of the newly synthesized 1,2,4triazolo[3,4-b][1,3,4]thiadiazoles for cancer cells. The study showed a good correlation between molecular docking and in vitro results for synthesized compounds towards the EGFR tyrosine kinase receptor protein.