Synthesis and Biological Evaluation of 1,2,4-Triazole and 1,3,4-Thiadiazole Derivatives as Potential Cytotoxic Agents

• Published in: Chemical & pharmaceutical bulletin Vol. 61; no. 11; pp. 1099 - 1104
• Main Authors: Song, Xue-Jiao, Shi, Yao-Jie, Li, Xiao, Ye, Ting-Hong, Yu, Luo-Ting, Xiong, Ying
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.11.2013; Pharmaceutical Society of Japan; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: 1,2,4-triazole; 1,3,4-thiadiazole; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - toxicity; Cell Line, Tumor; Cell Survival - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; cytotoxicity; DNA replication; DNA Replication - drug effects; Drug Screening Assays, Antitumor; HCT116 Cells; Humans; Life Sciences & Biomedicine; Pharmacology & Pharmacy; Physical Sciences; Science & Technology; Structure-Activity Relationship; Thiadiazoles - chemical synthesis; Thiadiazoles - chemistry; Thiadiazoles - toxicity; Triazoles - chemical synthesis; Triazoles - chemistry; Triazoles - toxicity; 1,3,4-thiadiazole; DNA replication; 1,2,4-triazole; cytotoxicity
• ISSN: 0009-2363; 1347-5223; 1347-5223
• DOI: 10.1248/cpb.c13-00242

A series of new 3-amino-5-sulfanyl-1,2,4-triazole and 2-amino-5-sulfanyl-1,3,4-thiadiazole derivatives have been synthesized and their cytotoxicities were evaluated on a panel of human cancer cell lines (BxPC-3, H1975, SKOV-3, A875, HCT116, etc.). The best one (compound 5m) exhibited activities with IC50 values ranging from 0.04 to 23.6 µ M against nine human cancer cell lines. Further biological evaluation indicated that DNA replication was blocked by treatment with compound 5m in HCT116 cells.