Heterocyclic Derivatives Bearing 4-Pyridyl Substituents; Multitarget Biological Evaluation

This study focuses on the multitarget biological evaluation of variously substituted 4-pyridyl thiosemicarbazones. Six compounds (C1-C6) containing chlorine atoms in different positions of the phenyl ring were synthesized, and their structures were confirmed using mass spectrometry, FTIR, and NMR spectroscopy. Biological evaluation included antioxidant activity assays (ABTS, DPPH, and ORAC-FL), antibacterial testing against Gram-positive and Gram-negative bacteria, and anticancer activity assessment against a panel of cancer cell lines (A375, G-361, LNCaP, Caco-2, and U-87 MG), as well as healthy fibroblasts (BJ) to evaluate selectivity. While the compounds exhibited limited antibacterial activity, more pronounced anticancer effects were observed, particularly for a singly chlorinated derivative, with reduced cytotoxicity toward healthy cells. No direct correlation was observed between anticancer and antioxidant activities. Finally, ADME analysis suggested favorable pharmacokinetic profiles for all six compounds.