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

Abstract

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.