ABSTRACT A novel series of ( E )‐ N '‐((1,3‐substituted diphenyl‐1H‐pyrazol‐4‐yl)methylene) picolinohydrazide derivatives ( 6a–6t ) was designed and synthesized via condensation of picolinohydrazide with 1,3‐disubstituted pyrazole‐4‐carbaldehydes. The molecular design was based on the hybridization of two privileged pharmacophores, namely the pyrazole scaffold and the picolinohydrazide moiety, to integrate kinase‐inhibitory and metal‐chelating features into a single molecular framework. The structures of the synthesized compounds were confirmed using IR, 1 H NMR, 1 3 C NMR, and HRMS techniques. The in vitro antiproliferative activity of the synthesized derivatives was evaluated by the sulforhodamine B (SRB) assay against MCF‐7 (breast cancer) and A549 (lung cancer) cell lines, using Adriamycin as a reference drug. Several compounds exhibited moderate cytotoxic activity, with compounds 6g , 6j , 6n , and 6o showing the most promising growth inhibitory effects. These derivatives displayed GI 50 values in the range of 31.9–56.3 µg/mL (approximately 69–115 µM), indicating their potential as lead structures for further optimization. Molecular docking studies were performed against a panel of cancer‐related targets, including AKT1 and KDM5A receptors. The most active compounds demonstrated favorable binding affinities toward both targets, suggesting a possible dual‐target mechanism involving modulation of PI3K/AKT signaling and epigenetic regulation pathways. Overall, this study identifies pyrazole–picolinohydrazide hybrids as promising lead scaffolds for the development of new anticancer agents.
Kumari et al. (Sun,) studied this question.