Metabolism of a potent neuroprotective hydrazide.

Using a drug discovery scheme for Alzheimer's disease (AD) that is based upon multiple pathologies of old age, we identified a potent compound with efficacy in rodent memory and AD animal models. Since this compound, J147, is a phenyl hydrazide, there was concern that it can be metabolized to aromatic amines/hydrazines that are potentially carcinogenic. To explore this possibility, we examined the metabolites of J147 in human and mouse microsomes and mouse plasma. It is shown that J147 is not metabolized to aromatic amines or hydrazines, that the scaffold is exceptionally stable, and that the oxidative metabolites are also neuroprotective. It is concluded that the major metabolites of J147 may contribute to its biological activity in animals.

[Determination of flavones in different origin and parts of Bupleurum smithii var. parvifoliaum by UPLC-PDA].

An ultra performance liquid chromatography method has been developed for determination of flavones in different origin and different parts from Bupleurum smithii var. parvifoliaum. The separation was performed at 30 degrees C on an Acquity UPLC BEH C18 column eluted with methanol and 0.1% phosphoric acid solution as mobile phases in gradient elution. The detection wavelength was set at 256 nm and the flow rate was 0.4 mL x min(-1). There flavones of rutin, quercetin and isorhamnetin were separated well, the linear calibration curves were obtained over the ranges of 0.106-1.06 microg for rutin (r = 0.999 8, n = 6), 0.004 87-0.048 7 microg for quercetin (r = 0. 999 7, n = 6), 0.022 0-0.220 microg for isorhamnetin (r = 0.999 8, n = 6). The mean recoveries of the three compounds were 99.3%, 97.8%, 98.9% with RSD of 2.4%, 3.0%, 3.2%. The result showed that the method is convenient and feasible for determination of the flavone content in B. smithii var. parvifoliaum.