Synthesis and biological evaluation of 3,4-diaryl-5-aminoisoxazole derivatives.
A series of cis-restricted 3,4-diaryl-5-aminoisoxazoles have been synthesized and evaluated for their biological activities. Among them, compound 11a and 13a displayed potent cytotoxic activities in vitro against five human cancer cell lines with IC(50) values in the low micromolar range and two compounds inhibited tubulin polymerization with IC(50) value of 1.8, and 2.1 microM, respectively, similar to that of CA-4. Compound 13a could arrest at the G2/M phase of the cell cycle at the concentration of 0.1 and 1.0 microM and induce apoptosis at 0.1-1.0 microM.
Liu
Tao
T
ZJU-ENS Joint Laboratory of Medicinal Chemistry, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Dong
Xiaowu
X
Xue
Na
N
Wu
Rui
R
He
Qiaojun
Q
Yang
Bo
B
Hu
Yongzhou
Y
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D003198:Computer Simulation; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D050257:Tubulin Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D000970:Antineoplastic Agents; D007555:Isoxazoles; D050257:Tubulin Modulators