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

Abstract

A series of N-alkyl tethered C-5 functionalized bis-isatins were synthesized and evaluated for antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed the compound 4t, 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 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. The 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 isatin is non-toxic to humans, presents a new possible scaffold for drug discovery against these important protozoal pathogens of humans and animals.

Isatin dimers and their biological activities

“…The majority of alkyl‐tethered isatin dimers 41 (Figure 8) were active against T. vaginalis and Giardia lamblia ( G. lamblia ) with 80.69–100% growth inhibitory at the concentration of 50 μM, but all of them except compounds 41a–c were inactive against Entamoeba histolytica ( E. histolytica ). [ 97 ] Among them, dimer 41c with 100% growth inhibitory against T. vaginalis, G. lamblia , and E. histolytica at the concentration of 50 μM was also active against Naegleria fowleri ( N. fowleri ), and the activity (IC 50 : 14.8 μM) was 3.6 times higher than that of miltefosine (IC 50 : 54.5 μM) against N. fowleri .…”

Isatin Derivatives with Potential Antitubercular Activities

“…Dimeric compounds usually display some unique properties such as enhanced biological activities, compared with their corresponding monomeric counterparts . Isatin dimers have demonstrated interesting biological profiles , therefore they are attractive building blocks for development of new anti‐TB agents.…”

Design, Synthesis, and In Vitro Anti‐Tumor Activities of 1,2,3‐triazole‐tetraethylene Glycol Tethered Heteronuclear Bis‐Schiff Base Derivatives of Isatin

“…Recently, isatin dimers were found to possess promising anticancer potential and have been widely studied . The structure–activity relationship (SAR) revealed that the linker and the noncovalent interactions are crucial for the biological activities of isatin dimers . 1,2,3‐Triazole and tetraethylene glycol can exert various noncovalent interactions, so the isatin dimers tethered through 1,2,3‐triazole‐tetraethylene glycol may have promising anticancer activity.…”