Development of novel isatin thiazolyl-pyrazoline hybrids as promising antimicrobials in MDR pathogens

Abstract

Microbial Multidrug Resistance (MDR) is an emerging global crisis. Derivatization of natural or synthetic scaffolds is among the most reliable strategies to search for and obtain novel antimicrobial agents for the treatment of MDR infections. Here, we successfully manipulated the synthetically flexible isatin moieties to synthesize 22 thiazolyl-pyrazolines hybrids, and assessed their potential antimicrobial activities in vitro against various MDR pathogens, using the broth microdilution calorimetric XTT reduction method. We chose 5 strains to represent the major MDR microorganisms, viz: Methicillin-resistant S. aureus (MRSA), and Vancomycin-resistant E. faecalis (VRE) as Gram-positive bacteria; Carbapenem-resistant K. pneumonia (CRKP), and Extended-spectrum beta-lactamase E. coli (ESBL-E), as Gram-negative bacteria; and Fluconazole-resistant C. albicans (FRCA), as a yeast-like unicellular fungus. The cytotoxicity of compounds 9f and 10h towards mammalian lung fibroblast (MRC-5) cells demonstrated their potential satisfactory safety margin as represented by their relatively high IC₅₀ values. The target compounds showed promising anti-MDR activities, suggesting they are potential leads for further development and in vivo studies.