Analysis of DNA protection, interaction and antimicrobial activity of isatin derivatives.

Isatin, thiosemicarbazone and their derivatives have been widely used in biological applications such as antimicrobial, antiviral and anticancer therapies. Herein, eight isatin and thiosemicarbazone derivative compounds were re-synthesized and evaluated for DNA binding analysis including DNA protection studies using plasmid DNA (pUC19) and DNA interaction experiments using calf thymus DNA (CT-DNA). All compounds were also utilized in vitro assay to assess the antimicrobial activity of compounds against different pathogenic bacterial strains. All isatin and thiosemicarbazone derivative compounds exhibited DNA protection activity which ranged from 23.5 to 59.5%. Among them, I3-(N-2-MP)-TSC had the greatest DNA protective activity. For DNA binding analysis, all compounds had the same constant concentration (40 µM), which interacts with CT-DNA. It was also observed that DNA interactions gave a high intrinsic binding constant (Kb = 1.72 × 104 M-1-9.73 × 105 M-1). Besides, several derivatives of isatin thiosemicarbazone exhibited significant and selective antibacterial activity with low concentration. These compounds primarily affected Gram-positive bacteria, but were not effective against P. vulgaris and E. coli. The Gram-positive methicillin-resistant S. aureus ATCC 43300 (MRSA) was the most influenced strain by these compounds. It was found that methyphenyl group at isatin was essential for its antibacterial activity for MRSA.