Synthesis of Isatin Derivatives Exhibiting Antibacterial, Antifungal and Cytotoxic Activities

Abstract

Objective: The current objective was to synthesize biologically active Isatin derivatives. For this purpose, six (06) chemical entities of Isatin derivatives such as 3a-3c and 4a-4c were synthesized from Isatin substrate.

Methods: The pure compounds were characterized with the help of ¹H-NMR, FT-IR, EIMS spectroscopic techniques. The synthesized amines 3a-3c and hydrazones 4a-4c were evaluated for their toxicity potential with the help of brine shrimp bioassay.

Results: The obtained results revealed that 3c exhibited promising toxicity (LD₅₀ = 1.03 × 10^-5 M) against Artemia salina. The pure chemical entities such as compounds 3a-3c and 4a-4c were evaluated against four Gram-negative (E. coli, P. aeruginosa, S. typhi, S. flexneri) and two Gram-positive (B. subtilis, S. aureus) bacteriae. The compound 3a displayed significant activity against two bacterial strains; i.e. P. aeruginosa, S. typhi, compound 3c demonstrated significant activity against P. aeruginosa. Compound 4b was the most active against S. typhi, displaying a greater diameter of the growth of inhibition zone (GIZ) than the standard drug. Compound 4c exhibited significant activity against P. aeruginosa and S. typhi. Compounds 3a-3c and 4a-4c exhibited moderate to significant antibacterial activity against three out of five strains. Only Compound 3c revealed promising toxicity (LD₅₀ = 1.03 × 10^-5 M) against Artemia salina. Antifungal studies of the compounds 3a-3c and 4a-4c against six fungal cultures; T. longifusus, C. albicans, A. flavus, M. canis, F. solani, and C. glabrata. All the compounds were active against one or more pathogens having inhibition (10- 90 %). Compound 3a exhibited significant inhibition i.e. 90 % against M. canis, 70 % against T. longifusus, compound 4b further displayed significant inhibition (90 %) against A. flavus and thus proved to be the most active member of the series.

Conclusion: All compounds showed better antibacterial, antifungal and cytotoxic activities, which may provide a ground to prepare enhanced molecules with much higher antibacterial activities.

Keywords: ¹HNMR; FT-IR; Isatin derivatives; antibacterial activity; antifungal activity; cytotoxicity; mass; synthetic strategy.