目的:设计合成系列liguzinediol的芳酸单酯前药,通过理化性质和人体血浆酶解特性研究,筛选出适合liguzinediol口服给药的候选前药。方法:以吡啶催化的酰氯与醇的酯合成法及DMAP催化的酸与醇的DCC缩合法,共合成6个liguzinediol的芳酸单酯类前药,用红外、质谱、核磁共振氢谱和碳谱进行结构确认。采用高效液相色谱法测定化合物的容量因子、溶解度、p H 7.4的化学稳定性以及体外80%人血浆中酯酶水解的释放特性。结果:liguzinediol的糠酸单酯、3-氯苯甲酸单酯与苯甲酸单酯血浆酶解速率过快;4-二甲氨基苯甲酸单酯化学稳定性较差;4-甲氧基苯甲酸单酯化学稳定性高,酶解释放速率适中。结论:liguzinediol的4-甲氧基苯甲酸单酯化学稳定性较高,体外80%人血浆酶解liguzinediol释放速率合适,可以作为liguzinediol口服给药形式的候选药物前体。
OBJECTIVE Liguzinediol is a derivative of the natural active ingredient ligustrazine,and we found that liguzinediol has significant positive inotropic effects,which are stronger than that of TMP.Besides,it does not lead to arrhythmia,hypotension and other side effects.This study aims to investigate the anti-apoptotic effects of liguzinediolon H9C2 cells.METHODS Apoptotic H9C2 cells induced by DOX were observed by electron microscope and FCM analysis.The protein expressions of Bax,Bcl-2,caspases 3 and NF-κB were detected by Western blotting.RESULTS Apoptotic H9C2 cells induced by DOX were observed,but without apoptotic bodies in liguzinediol group.Declined peak of H9C2 cell apoptosis was seen in liguzinediol group by FCM analysis.And downregulation of Bax,caspases 3,NF-κB and upregulation of Bcl-2 were found by Western blotting.CONCLUSION Liguzinediol protected cardiomyocytes against apoptosis through downregulation of Bax and caspases 3 and upregulation of Bcl-2.Liguzinediol can inhibited cardiomyocyte apoptosis through the NF-κB signal pathway.
