Design, synthesis and biological evaluation of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives.
Based on our previous work, a series of novel 3-alkylsulfanyl-4-amino-1,2,4-triazole derivatives were designed, synthesized and evaluated for their antiproliferative activities. The results indicated that some compounds possessed significant antiproliferative activities against four cancer cell lines, HepG2, HCT116, PC-3, and Hela. Particularly, the most promising compound 8d displayed 184-, 18-, and 17-fold improvement compared to fluorouracil in inhibiting HCT116, Hela and PC-3 cell proliferation with IC50 values of 0.37, 2.94, and 31.31μM, respectively. Most interestingly, the compound did not affect the normal human embryonic kidney cells, HEK-293. Moreover, mechanistic investigation showed that the representative compound 8d induced apoptosis and blocked cell cycle in G2/M phase in Hela cells in a dose-dependent manner. These findings suggest that compound 8d may have potential to be developed as a promising lead for the design of novel anticancer small-molecule drugs.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: plzhao@smu.edu.cn.
Pei-Liang
PL
Zhao
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Peng
P
Chen
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Qiu
Q
Li
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Meng-Jin
MJ
Hu
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Peng-Cheng
PC
Diao
School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, PR China.
En-Shan
ES
Pan
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China. Electronic address: youww@smu.edu.cn.
Wen-Wei
WW
You
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D057809:HEK293 Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D014230:Triazoles; C045575:1,2,4-triazole
1,2,4-Triazole; Alkylsulfanyl; Antiproliferative activity; Synthesis