A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer: synthesis and its cytotoxic activity.
A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer was designed, synthesized and evaluated for its cytotoxic activity against five human cancer cell lines and the cytotoxicity against human normal liver cell L-02. Compound 3 showed excellent cytotoxic activity and good selectivity between cancer and normal cells. Further mechanistic studies revealed that treatment of EC109 cells with compound 3 caused an obvious G2/M arrest in a concentration- and time-dependent manner and induced apoptosis probably through the mitochondrial pathway accompanied with the decrease of mitochondrial membrane potential, activations of caspase-9/-3, cleavage of MDM2 as well as up-regulation of the expressions of p53 and Bax.
School of Pharmaceutical Sciences and New Drug Research & Development Center, Zhengzhou University, Zhengzhou 450001, PR China.
Bin
B
Yu
Xiao-Jing
XJ
Shi
Yong-Fei
YF
Zheng
Yuan
Y
Fang
En
E
Zhang
De-Quan
DQ
Yu
Hong-Min
HM
Liu
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D019281:Dimerization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013256:Steroids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
C419143:1,2,4-triazole(1,5a)pyrimidine; D000970:Antineoplastic Agents; D011743:Pyrimidines; D013256:Steroids; D014230:Triazoles
Apoptosis; Cell cycle arrest; Cytotoxicity; Mitochondrial pathway; Steroid dimer; [1,2,4] Triazolo [1,5-a] pyrimidine