Development of novel 1,4-Dihydropyridine-tethered Isatin scaffolds as potential candidates for the treatment of Cancer and fungal infections.

The pursuit of novel therapeutic agents with potent anticancer activity remains a key priority in medicinal chemistry, particularly for addressing liver and stomach malignancies, which continue to present substantial clinical challenges. In this study, we have reported the synthesis and biological assessment of a new series of novel 1,4-Dihydropyridine (DHP) tethered Isatin scaffolds, aimed at identifying promising candidates with significant anticancer potential. A combined approach of in-silico ADMET analysis, molecular docking and in-vitro cytotoxic screening was employed. The ADMET predictions indicated favorable pharmacokinetic profiles and minimal toxicity for most of the compounds. Molecular docking revealed strong binding with CDK2, supporting their anticancer potential. Compounds P3, P6, P7, P10, P11, and P12 demonstrated substantial anticancer activity against HepG2 (liver cancer) and AGS (gastric cancer) cell lines when compared to cisplatin, with P11 being the most potent (IC50 = 18.61 μM for HepG2 and 26.55 μM for AGS). Additionally, antifungal evaluation revealed only marginal activity against A. fumigatus 3007. These findings establish 1,4-DHP-isatin hybrids as promising lead compounds for further development in anticancer and antifungal drug discovery.