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Journal of Chemistry
Volume 2014, Article ID 897141, 7 pages
Research Article

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

1Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
2Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia
3Stem Cell & Tissue Re-Engineering Program, Research Center, King Faisal Specialized Hospital & Research Center, MBC-03, P. O. Box 3354, Riyadh 11211, Saudi Arabia

Received 9 April 2014; Revised 21 May 2014; Accepted 26 May 2014; Published 18 June 2014

Academic Editor: Xinyong Liu

Copyright © 2014 Mashooq Ahmad Bhat et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 × 105μg/mL).