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

Abstract

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.

Keywords

Pyridine / Isoxazole / Anticancer activity / Chemotherapeutic agent

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