Synthesis of some new pyrene-based hydrazinyl-thiazole derivatives via a one-pot strategy: biological evaluation and molecular docking studies.

In this study, we report a streamlined one-pot synthesis of a new series of (E)-4-phenyl-2-(2-(pyren-1-ylmethylene)hydrazinyl)thiazole derivatives (4a-4o). The reaction involves the condensation of pyrene-1-carbaldehyde, thiosemicarbazide, and α-halo ketones in the presence of a catalytic amount of InCl3 as a Lewis acid catalyst, carried out under reflux in a (1 : 1, v/v) H2O/EtOH medium at 80 °C. This protocol provides several key advantages, including mild reaction conditions, short reaction times, excellent yields, broad functional group tolerance, and the added benefit of chromatography-free product isolation, thereby enhancing practicality and operational simplicity. All synthesized compounds were fully characterized using 1H NMR, 13C NMR, FT-IR spectroscopy, and LC-MS analysis. The anticancer potential of the synthesized derivatives was evaluated against the human breast cancer cell line (MCF-7) using an in vitro MTT assay. Compounds 4m and 4g exhibited the most promising cytotoxic effects, displaying IC50 values of 43.66 and 45.24 µg mL-1, respectively. Furthermore, molecular docking studies were performed to elucidate structure-activity relationships, revealing a strong correlation between the predicted binding affinities and the experimental biological outcomes.