Design synthesis and preliminary antimicrobial evaluation of N-alkyl chain-tethered C-5 functionalized bis-isatins

摘要

A series of N-alkyl-tethered C-5 functionalized bis-isatins were synthesized and evaluated for their antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed compound >4t, with an optimal combination of a bromo substituent at the C-5 position of the isatin ring and a propyl chain linker, being the most active among the synthesized series exhibiting an IC50 value of 3.72 μM against Trichomonas vaginalis while >4j exhibited an IC50 value of 14.8 μM against Naegleria fowleri, more effective than the standard drug miltefosine. Compound >3f with an octyl spacer length was the most potent among the series against Giardia lamblia with an IC50 of 18.4 μM while >3d exhibited an IC50 of 23 μM against Entamoeba histolytica. This library was also screened against the fungal pathogen Aspergillus parasiticus. 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 found isatin to be non-toxic to humans, presents a new possible scaffold for drug discovery against these important protozoal pathogens of humans and animals.