Study On The Design, Synthesis And Bioactivity

Cerebrovascular disease has become a serious hazard to human health, particularly in situation of ischemic cerebrovascular disease, however, no effective drugs has been found so far. Thus the effort to discover active molecules from new lead is theoretically and practically extremely significant for etiological study of cerebrovascular mechanism, and for validation of disease target for cerebrovascular treatment, and even for development of drug candidates.(-)-Linaria acid (LA) is an optical natural product isolated from the ethanol extract of the whole herb of L. vulgaris Mill. Linaria acid may have potential activities of cardio-and cerebro-vascular according to the prediction results by PASS (Prediction of Activity Spectra for Substances) and drug-likeness evaluation (rule of five).Based on the lead compound Linaria acid,22 new derivatives were synthesized through four different synthetic routes from the start material of substituted benzaldehydes. Their structures were identified by ESI-MS,1H-NMR, specific rotation and melting point. The trans configuration of C=C compounds were confirmed by combining molecular simulation and 1H, ’H-NOESY sepctroscopy.Finally, the six Linaria acid derivatives (TY-01、TY-02、TY-03、TY-04、TY-05 and TY-06) were evaluated with a preliminary anti-ischemic experiment in vitro. Activity test results showed that TY-03-06 can inhibit the aged liver MDA content with dose-dependent, and thus own anti-ischemic activity. Four compounds presented better potent than the lead compounds Linaria acid. According to their IC50 values their active rank is TY-06, TY-05, TY-03, TY-04, LA. The activity evalution of the other compounds is still underway.