| Summary: | 碩士 === 長庚大學 === 天然藥物研究所 === 97 === In previous studies, 3,4-methylenedioxy-β-nitrostyrene (MNS) and 4-O-benzoyl-3-methoxyl-β-nitrostyrene (BMNS) exhibited inhibitory effector platelet aggregation via suppression of tyrosine kinases (Src and Syk). Furthermore, BMNS possessed 8 times greater potency than MNS, and 100 times greater potency than non-selective tyrosine kinases inhibitors (genistein and tyrphostin A47) in inhibiting thrombin-induced pletlet aggregation. Accordingly, β-nitrostyrenes derivatives were be as potential anti-platelet aggregation agent. In order to research and develop potent antiplatelet β-nitrostyrenes, we designed and synthesized a series of β-nitrostyrenes derivatives and evaluate their anti-platelet activities. On the basis of their bioactivities, the proposed structure-activity relationships(SARs) were as following.
1. All of the synthesized or commercial β-nitrostyrene derivatives inhibited platelet aggregation induced by thrombin or collagen.
2. For the compounds of Series A, the substitutes on the B ring influence the bioactivity. Of these, the derivatives with the para- substitutes are more potency.
3. For the compounds of Series B,
a. When the benzene ring (A ring) was replaced by thiophenyl or furanyl ring, (ex CYT-RX17 and CYT-RX18), the activity was decreased.
b. While the part of A ring in para-position is changed to hydroxyl group , the activity decreases.
c. While the para-hydroxyl group in the A ring was modified by its isoteres (e.g. Cl or CH3), or other groups (e.g. NO2 or OCH3), the activity all increases.
d. The bioactivities of β-methyl-β-nitrostyrenes (CYT-RX20 and CYT-RX22) were less then β-nitrostyrenes (CYT-RX19 and CYT-RX21).
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