Synthesis of New [1,2,4]Triazolo[3,4-b][1,3,4]thiadiazines and Study of Their Anti-Candidal and Cytotoxic Activities

Abstract EN

New triazolothiadiazine derivatives 5a–h were synthesized from 4-amino-3-(4-pyridyl)-5-mercapto-4H-1,2,4-triazole (3) with substituted aryl hydrazonoyl chlorides 4a–h.

The compounds were tested in vitro against eleven Candida species and compared with standard drug ketoconazole.

Among these compounds, the compounds bearing p-chlorophenyl 5e, p-methoxyphenyl 5c, phenyl 5a, and p-sulphonamidophenyl 5g substituents on triazolothiadiazine system were found to be the most effective derivatives against Candida species.

Compound 5e was the most effective compound against C.

parapsilosis (ATCC 22019), C.

albicans (ATCC 66027), C.

specie [blood] 12810, and C.

specie [urine] 300 with MIC value of 6.25 μg/mL, whereas ketoconazole exhibits the inhibitory activity with MIC value of 3–30 μg/mL against all tested strains.

It was clear that there is a positive correlation between anti-Candidal activity and p-chlorophenyl substitution on triazolothiadiazine ring.

All the synthesized compounds were also investigated for their potential cytotoxicity on noncancer cell line (MCF-12) using WST-1 assay.

Three compounds 5d, 5a, and 5h were found to have the same IC50 value as that of standard drug ketoconazole against noncancer cell line MCF-12 (IC50 ≥ 1.0 × 105 μg/mL).