Synthesis and Mechanism Studies of Novel Radioprotectants

• Main Authors: Chiang Chih-Chia, 姜治家
• Other Authors: Tsai Hou-Jen
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/13072973833708984875

博士 === 國防大學中正理工學院 === 國防科學研究所 === 96 === ABSTRACT The works in this research concentrate on the design and organic synthesis of three categories of chemical agents: (1) sulfur-containing cinnamate derivatives (5a-7b). (2) caffeic acid phenyl ester analogues (9a-10c) with build in oxygen, sulfur, and selenium atom, correspondingly. And (3) bis-coumarin derivatives (17-20, 23a-24c). All the prepared compounds have been assayed to evaluate their bioactivities on radioprotection, ABTS free radical scavenging, and matrix metallo protease 2 and 9 (MMP-2, MMP-9) inhibition. The experimental results show that many compounds in category (1) and (3) contain radio-protective effect on cell culture under exposure 8 Gy radiation. Among them, 5b and 24c are the most potent agents with protection factor (PF) values of 1.34 and 1.28 respectively. It is of interest that compounds in category (2) demonstrate no effect on radioprotection. On the contrary 10c in category (2) produces sensitive result with a PF value of 0.20. As to ABTS free radical scavenging effect, compounds in category (1) and (2) are less active than known potent radical scavenger Trolox while compounds 23a, 27a, 27b in category (3) are superior to Trolox. It is well known that both MMP-2 and MMP-9 are induced when cells expose under radiation. The induced MMP-2 and MMP-9 then hydrolyze cell matrix and cause cell damage. Among prepared compounds, certain compounds in category (1) illustrate better inhibition against MMP-2, and some compounds in category (2) and (3) demonstrate better inhibition against MMP-9. Our bioactive results will be helpful for further design novel compounds with improve activity on radioprotection, ABTS free radical scavenging, and matrix MMP-2 and MMP-9 inhibition.