Synthesis and Antimicrobial Activity of 3-Alkylidene-2-Indolone Derivatives

The escalating threat of antibiotic-resistant bacteria and fungi underscores an urgent need for new antimicrobial agents. This study aimed to synthesize and evaluate the antimicrobial activities of two series of 3-alkylidene-2-indolone derivatives. We synthesized 32 target compounds, among which 25 exhibited moderate to high antibacterial or antifungal activities. Notably, compounds <b>10f</b>, <b>10g</b>, and <b>10h</b> demonstrated the highest antibacterial activity with a minimum inhibitory concentration (MIC) of 0.5 μg/mL, matching the activity of the positive control gatifloxacin against three Gram-positive bacterial strains: <i>Staphylococcus aureus</i> ATCC 6538, 4220, and Methicillin-resistant <i>Staphylococcus aureus</i> ATCC 43300. Moreover, the three most active compounds <b>10f</b>, <b>10g</b>, and <b>10h</b> were evaluated for their in vitro cytotoxicity in the HepG2 cancer cell line and L-02; only compound <b>10h</b> was found to exert some level of cytotoxicity. These findings suggest that the synthesized 3-alkylidene-2-indolone derivatives hold potential for further development as antibacterial agents.