Novel Isatin-Chalcone Derivatives: Synthesis, Characterization and Evaluation for Antimicrobial and Anticancer Applications

A series of novel isatin-chalcone hybrids (IA-IM) were synthesized via a microwave-assisted method and evaluated for their antimicrobial, antifungal, antitubercular and anticancer activities. The compounds were characterized using spectroscopic techniques and screened for antibacterial activity against Staphylococcus aureus and Escherichia coli, antifungal activity against Candida albicans and Aspergillus niger, antitubercular activity against Mycobacterium tuberculosis H37Rv and cytotoxicity against breast (MCF-7) and cervical (HeLa) cancer cell lines. Compounds IK (4-NH2), IF (2-Cl) and IL (2-F) exhibited potent antibacterial activity, with zones of inhibition (ZOI) comparable to or exceeding amikacin at higher concentrations. Against fungal strains, IM (4-NO2), IK (4-NH2) and IL (2-F) demonstrated significant activity, approaching the efficacy of fluconazole. In antitubercular assays, compounds ID (2-F), IE (3,4-OCH3), IF (2-Cl) and IG (4-Cl) showed sensitivity at 12.5-25 µg/mL. Anticancer evaluations revealed that compounds IH (4-Br), IK (4-NH2) and IE (3,4-OCH3) were highly potent against MCF-7 and HeLa cells, with IC50 values as low as 6.53 ± 1.12 µM, while sparing normal HEK-293 cells. Structure-activity relationship (SAR) studies highlighted the importance of electron-donating groups (e.g. -NH2, -OCH3) and halogen substitutions (e.g. -Cl, -Br) in enhancing biological activity. These findings demonstrate the potential of isatin-chalcone hybrids as multi-functional therapeutic agents, providing a foundation for further optimization and development.