Vol. 7, Issue 10, Part A (2025)

Chalcone and isatin scaffolds are widely recognized as privileged pharmacophores in medicinal chemistry because of their diverse biological activities. In this study, a new series of chalcone-linked isatin derivatives was synthesized and evaluated for cytotoxic and antimicrobial activities with the aim of identifying potent dual-action agents. The synthetic pathway involved N-alkylation of indoline-2,3-dione followed by nucleophilic addition at the C-3 position with various acetophenone analogues, yielding 3-hydroxy-3-(2-oxoethyl)-1-(3-phenylpropyl)indolin-2-one derivatives, which were further dehydrated to obtain (Z)-3-(2-oxoethylidene) derivatives. The structures of the synthesized compounds were confirmed by IR, NMR, and mass spectrometry. Antibacterial screening was carried out using the cup-plate method against Gram-positive (Bacillus subtilis, Staphylococcus aureus) and Gram-negative (Escherichia coli, Salmonella typhi) strains, with Ciprofloxacin as the standard. Several halogen-substituted derivatives demonstrated pronounced inhibition zones comparable to the standard drug. Cytotoxic activity was assessed by MTT assay against MDA-MB-231 (human breast adenocarcinoma) and A549 (human lung carcinoma) cell lines. IC₅₀ values indicated that derivatives such as 168i, 210b, and 248c exhibited significant cytotoxicity, with compound 210b being most effective against MDA-MB-231 and 248c showing high activity against A549. Nearly half of the most potent derivatives contained halogen substituents, suggesting that halogenation enhances cytotoxic and antimicrobial potential. Overall, the study highlights chalcone-linked isatin derivatives as promising scaffolds for the development of novel anticancer and antimicrobial agents.