Abstract
AimTo search for novel nitric oxide (NO) releasing anti-tumor agents, a series of furoxan-based nitric oxide-releasing derivatives of 1-oxo-oridonin were designed and synthesized. MethodDifferent furozan-based NO donors (9a-i) were synthesized and conjugated with the 14-hydroxyl of 1-oxo-oridonin (2). The level of nitrate/nitrite in the cell lysates was tested by Griess assay and the anti-proliferative activity of these derivatives against four human cancer cell lines was also determined. ResultsThese furoxan-based NO-releasing derivatives could produce more than 19 μmol·L−1 of NO in vitro at the time point of 60 min. The most promising compound 10 h exhibited stronger activity than the positive control Taxol against the Bel-7402 cell line with an IC50 value 0.74 μmol·L−1. The structure-activity relationships were concluded based on the derived experimental data. ConclusionThese results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel anti-tumor agents.
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