Jalilian A R, Sattari S, Bineshmarvasti M, Shafiee A, Daneshtalab M
Department of Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Iran.
Arch Pharm (Weinheim). 2000 Oct;333(10):347-54. doi: 10.1002/1521-4184(200010)333:10<347::aid-ardp347>3.0.co;2-6.
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.
耐药真菌病原体在临床上的重要性日益增加，这使得微生物学和抗真菌研究更加紧迫。合成了各种噻唑并（或1,2,3 - 噻二唑并）硫代氨基脲（2a - 2e）、3 - 硫代 - 1,4 - 二氢三唑并噻唑（或1,2,3 - 噻二唑）（3a - 3e）、它们的相关取代硫代 - 4H - 1,2,4 - 三唑（4a - 4p）和砜（5a - 5o）。测试的大多数化合物的抗真菌活性在0.53至12.5微克/毫升的MIC范围内对新型隐球菌和酿酒酵母表现出显著效果，而它们对白色念珠菌的活性中等，对烟曲霉的活性较弱。在10 ppm浓度下，除化合物4c和2c外，所有化合物对卤虫的毒性较低（存活率高于80%）。在100 ppm浓度下，除化合物2b、2e、3c、3d、3e和4e外，大多数化合物表现出毒性。化合物4b、4c和4h在0.1 mM浓度下对Kbalb细胞系表现出体外细胞毒性，化合物4c和4g对143B细胞系表现出体外细胞毒性。
