Novel thiadiazole-thiazole hybrids: synthesis, molecular docking, and cytotoxicity evaluation against liver cancer cell lines

Abstract

One of the worst diseases, cancer claims millions of lives each year throughout the world, necessitating the creation of novel treatments. In this study, we designed a novel series of 1,3,4-thiadiazoles through the reaction of 2-(4-methyl-2-(2-(1-phenylethylidene)hydrazineyl)thiazole-5-carbonyl)-N-phenylhydrazine-1-carbothioamide (3) with the proper hydrazonoyl halides. Using the MTT assay, the newly synthesized thiadiazoles' growth-inhibitory potential against the liver cancer cell line HepG2-1 was assessed. In comparison to the standard drug doxorubicin (IC50 = 0.72 ± 0.52 µM), the results showed that two compounds, 16b and 21 (IC50 = 0.69 ± 0.41 and 1.82 ± 0.94 µM, respectively) had promising anticancer activity. The structural activity relationship (SAR) was investigated. In addition, molecular docking analysis onto quinone oxidoreductase2 (NQO2) receptor (PDB: 4ZVM) was investigated against the potent compounds to examine the reliability of the in vitro results. The newly prepared thiadiazole-thiazole hybrids are therefore regarded as potent anticancer drugs.