Synthesis, preliminary structure-activity relationships and biological evaluation of pyridinyl-4,5-2H-isoxazole derivatives as potent antitumor agents

A series of novel pyridinyl-4,5-2H-isoxazole derivatives was synthesized and their chemical structures were characterized by 1H NMR, 13C NMR as well as MS spectroscopic methods, their melting points were also determined. The inhibitory effects of them against breast cancer cell line(MCF-7) were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide(MTT) procedure in vitro. Most of them possesed potent anti-proliferative activities, among which 11c and 11j exhibited half maximal inhibitory concentrations(IC50) of 1.9 and 1.5 μmol/L, respectively. These compounds also exhibited potent anti-proliferative activities against both human hepatoma cell line(HepG2) and cervical cancer cell line(Hela). Preliminary Structure-activity relationship(SAR) information from these compounds can be used to guide further exploration of new compounds with better potency as molecular probes. Further study on the mechanism-of-action of these compounds is under investigation.