Synthesis, biological evaluation and molecular docking studies of novel 1,3,4-thiadiazoles as potential anticancer agents and human carbonic anhydrase inhibitors.

Thiosemicarbazide and also 1,3,4-thiadiazole derivatives have been garnering substantial attention from researchers worldwide due to their expansive range of biological activities, encompassing antimicrobial, anti-inflammatory, and anticancer properties. Herein, we embarked on a comprehensive investigation in this study, introducing a novel series of thiosemicarbazides (3a-3i) and their corresponding 1,3,4-thiadiazole (4a-4i) derivatives. The compounds were meticulously designed, synthesized, and subjected to meticulous characterization using various spectroscopic methods such as FT-IR, 1H-NMR, 13C-NMR, and elemental analysis. Afterward, their potential anti-proliferative effectiveness was assessed using MTT assay against two cancer cell lines (U87 and HeLa) and normal fibroblast cells (L929). Among the compounds, 4d showed the highest cytotoxic activity against U87 and 4i against HeLa. Compound 3b exhibited selective cytotoxic activity against both cancer cells. Among the molecules with selective activity against the U87 cell line; 3a, 3b, 4d and 4e were further evaluated by caspase-3 activity levels, Bax and Bcl-2 protein expression, and total oxidant status assay. Besides, carbonic anhydrase IX activity studies were also performed in order to understand the underlying mechanism of action. The results indicated that compound 4e showed higher efficacy than standard acetazolamide (IC50 = 0.58 ± 0.02 µM) with an IC50 value of 0.03 ± 0.01 µM. Furthermore, molecular docking studies were carried out using carbonic anhydrase IX crystals to determine the compound's interactions with the enzyme's active sites. This comprehensive investigation sheds light on the intricate interplay between molecular structure and biological activity, providing valuable insights into the therapeutic potential of these compounds.

Novel imidazo[2,1-b]thiazole-based anticancer agents as potential focal adhesion kinase inhibitors: Synthesis, in silico and in vitro evaluation.

The purpose of this study was to synthesize imidazo[2,1-b]thiazole derivatives, characterize them with spectroscopical techniques and investigate for cytotoxic and apoptotic effects on glioma C6 cancer cell line. The in vitro anticancer activities were also investigated against focal adhesion kinase. Most of the compounds, particularly the derivatives carrying 3-oxo-1-tiya-4-azaspiro[4.5]decane moiety, exhibited higher or comparable activities in comparison with the reference drug, cisplatin. Compounds with methyl, propyl, phenyl moieties at the eighth and second position of the spirothiazolidinone ring showed high FAK inhibitory activities. In addition, molecular docking studies shed light on the binding modes of the synthesized compounds. The critical interactions with amino acid residues located in the active site were revealed. The results obtained from both biological assay data and computational results might provide insight into developing new inhibitors against focal adhesion kinase.