Synthesis and in vitro antifungal and cytotoxicity evaluation of thiazolo-4H-1,2,4-triazoles and 1,2,3-thiadiazolo-4H-1,2,4-triazoles

The increasing clinical importance of drug-resistant fungal pathogens has lent additional urgency to microbiological and antifungal research. Various thiazolo(or 1,2,3-thiadiazolo)thiosemicarbazides (2a-2e), 3-thiono-1,4-dihydrotriazolothiazoles-(or 1,2,3-thiadiazoles) (3a-3e), their related substituted thio-4H-1,2,4-triazoles (4a-4p) and sulfones (5a-5o) were synthesized. Most of the compounds tested for antifungal activity exhibited significant effects against Cryptococcus neoofrmans and Sacchromyces cerevisiae at MIC ranges of 0.53 to 12.5 micrograms/mL, whereas their activities were moderate against Candida albicans and weak against Aspergillus fumigatus. At 10 ppm concentration, all compounds showed low toxicity on brine shrimps (higher than 80% survival), except compounds 4c and 2c. At 100 ppm concentration most of the compounds showed toxicity except compounds 2b, 2e, 3c, 3d, 3e, and 4e. Compounds 4b, 4c, and 4h showed in vitro cytotoxicity against Kbalb cell lines and compounds 4c and 4g against 143B cell lines at 0.1 mM concentration.