Design, Synthesis and Preliminary Antimicrobial Evaluation of -Alkyl Chain Tethered C-5 Functionalized Bis-Isatins.

A series of -alkyl tethered C-5 functionalized bis-isatins were synthesized and evaluated for antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed the compound , with an optimal combination of bromo-substituent at the C-5 position of isatin ring along with propyl chain linker being most active among the synthesized series exhibiting an IC value of 3.72 μM against while exhibited an IC value of 14.8 μM against , more effective than the standard drug Miltefosine. The compound with an octyl spacer length was the most potent among the series against with an IC of 18.4 μM while exhibited an IC of 23 μM against . This library was also screened against the fungal pathogen . A number of the compounds demonstrated potency against this fungus, illustrating a possible broad-spectrum activity. Furthermore, an evaluation of these synthesized compounds against a panel of normal flora bacteria revealed them to be non-cytotoxic, demonstrating the selectivity of these compounds. This observation, in combination with previous studies that isatin is non-toxic to humans, presents a new possible scaffold for drug discovery against these important protozoal pathogens of humans and animals.