Synthesis, Characterization, Molecular Docking Study and Biological Evaluation of Novel 1,3,4-Thiadiazole-Based...

The design, synthesis, and biological assessment of new heterocyclic compounds containing the 1,3,4-thiadiazole moiety, a well-known pharmacophore with substantial medicinal significance, are the main topics of this study. To create a variety of thiadiazole-based heterocyclic systems, such as pyrazoles, triazoles, pyrimidines, and thiophenes, a novel cyanoacetohydrazide derivative was created and used as a crucial intermediate. IR, ¹H-NMR, ¹³C-NMR, and mass spectrometry were the spectroscopic methods used to confirm the structures of produced compounds. The synthesized compounds' biological properties were assessed for their potential as antioxidants and anticancer agents. Several derivatives showed impressive activity in cytotoxicity tests against HePG-2 and MCF-7 cancer cell lines, with several compounds showing greater potency than the reference medication 5-fluorouracil. Compounds 17, 18, and 13 exhibited the strongest anticancer activity, highlighting the significance of structural and electronic properties in improving biological performance. Furthermore, an assessment of the synthesized compounds' antioxidant activity revealed that they have differing levels of free radical scavenging activity, with compounds 17 and 18 exhibiting the most notable benefits, albeit still less than ascorbic acid. Electron-donating and electron-withdrawing groups, molecular conjugation, and lipophilicity all play a part in regulating antioxidant and anticancer actions, according to structure-activity relationship (SAR) studies. Additionally, substantial interactions between specific drugs and the EGFR tyrosine kinase domain were suggested by molecular docking studies, indicating their possible mode of action. All things considered, our work shows that thiadiazole-based heterocycles are attractive candidates for the creation of novel antioxidants and anticancer medicines and offers insightful information for future drug design.