Design, synthesis, and biological evaluation of novel alkylsulfanyl-1,2,4-triazoles as cis-restricted combretastatin A-4 analogues.
Thirty-two novel 3-alkylsulfanyl-1,2,4-triazole derivatives, designed as cis-restricted combretastatin A-4 analogues, were synthesized and evaluated for their antiproliferative activities. The results indicated that analogue 20 showed more potent antiproliferative activities against PC-3 cell lines than positive control CA-4. Particularly, the most promising compound 25 displayed 5-fold improvement compared to CA-4 in inhibiting HCT116 cell proliferation with IC50values of 1.15 μM. Further flow-activated cell sorting analysis revealed that compound 20 displayed a significant effect on G2/M cell-cycle arrest in a dose-dependent manner in PC-3 cells. From this study, analogues 20 and 25 were the most potent anti-cancer agents in this structural class, and were considered lead compounds for further development as anti-cancer drugs.
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Yan-Hong
YH
Li
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Bei
B
Zhang
Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Science, Southern Medical University, Guangzhou 510515, PR China.
Hai-Kui
HK
Yang
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.
Peng-Cheng
PC
Diao
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
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
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001632:Bibenzyls / Q000737:chemistry* / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D001632:Bibenzyls; D014230:Triazoles; C045575:1,2,4-triazole; C040105:combretastatin
Alkylsulfanyl-1,2,4-triazoles; Antiproliferative activity; Synthesis