Synthesis of Thiophene Derivatives as Potential Radiosensitizers and Antiinflammatory Agents

• Main Authors: Liang,Chu-Hua, 梁琡華
• Other Authors: An-Rong Lee,Wen-Hsin Huang
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/67817143543394589582

碩士 === 國防醫學院 === 藥學研究所 === 94 === Our laboratory previously carried out the design and synthesis of a series of benzothieno[2,3-c]quinolone derivatives to develop novel anticancer drugs in our laboratories. After screening of the radiosensitizer/radioprotectant, the results showed that benzothiophene intermediates had strong potency to enhance the activity of radiation. On the other hand, literatures indicated that some thiophene derivatives possess significant antiinflammatory activity. Therefore, we further designed and synthesized a series of benzothiophene and thiophene derivatives to develop novel highly effective and low toxic radiosensitizers/radioprotectants and antiinflammatory drugs. The starting materials, p-methoxycinnamic acid, benzo[b]thiophene-2-carboxylic acid, 2-thiophenecarboxylic acid, 3-(2-thienyl)acrylic acid, 2-thiopheneacetic acid, and 2,5-thiophenedicarboxylic acid, were respectively treated with excess thionyl chloride in toluene to the preparation of all the target compounds. After heating at reflux for 1-48 hours and being concentrated in vacuum, acyl intermediates without purification were further reacted with various anilines in the presence of triethylamine to afford the target compounds. The preliminary results showed that benzothiophene and thiophene derivatives revealed potent radiosensization, especially T3c (48.2 %) superior to others. However, the results of target compounds by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl) -2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay showed that none of the synthetic products were active against MCF-7 (breast carcinoma), NCI-H460 (lung cancer), or SF-268 (glioblastoma) cancer cell lines. On the other hand, compounds 5c、5d、M3c、T3c were much potent than ibuprofen after screening of the target compounds by carrageenan-induced paw edema model.