氯-胺基苯基-123四氢异喹啉二氯铂类及相关化合物的合成.DOC

1-(5-氯-2-胺基苯基)-1,2,3,4-四氫異喹啉二氯鉑類及相關化合物的合成 及生物活性評估研究 Synthesis and Biological Activity of [1-(5-Chloro-2-Aminophenyl)- 1,2,3,4-Tetrahydroisoquinoline] Dichloroplatinums and their Relative Compounds 研究生：陳勝利 Chen, Shen-Li 指導教授：黃卓治 Huang, Tzou-Chi 張誌益 Chang, Chi-I 【摘要】 本研究描述簡單方法製備1-(5-氯-2-胺基苯基)-1,2,3,4-四氫異喹啉類化合物。苯乙胺與氯醯類反應得N-苯乙醯胺(1a-c)，隨後以Bischler-Napieralski條件環化可得1-(5-氯-2-硝基苯基)-3,4-二氫異喹啉類(2a-c)。化合物 2a-c再以SnCl2·2H2O於乙酸乙酯下反應得1-(5-氯-2-胺基苯基)-3,4-二氫異喹啉類及10-氯-5,6-二氫吲唑 [3,2-a] 異喹啉類 (3a-c)，1-(5-氯-2-胺基苯基)-3,4-二氫異喹啉類以四氫硼化鈉於甲醇下處理得1-(5-氯-2-胺基苯基)-1,2,3,4-四氫異喹啉類 (4a-c)，所得所有四氫異喹啉與K2PtCl4反應得順-二氯鉑錯合物類 (5a-c)。 三種順-二氯鉑錯合物被合成，分別對人類的四種腫瘤細胞株抗腫瘤活性試驗。結果顯示，所合成的錯合物對乳癌皆有不錯的效果，對結腸癌效果亦佳。 本研究再以十五種合成藥物以紙錠試驗法評估其抗菌活性，經試驗結果得知五種合成藥物具抗菌活性，實驗證明5-氯-2-胺基苯基-1,2,3,4-四氫異喹啉之順二氯鉑錯合物其抗腫瘤與抗菌活性皆有不錯的表現，值得繼續研究發展。 關鍵字：異喹啉、肝癌、結腸癌、子宮頸癌、乳癌、生物活性、抗菌活性、 細胞毒性試驗。 【Abstract】 A simple approach to 1-(5-chloro-2-aminophenyl)-1,2,3,4-THIQs is described. Reaction of phenethylamines with acid chlorides led to N-phenylethylamides (1a-c). Cyclization of N-phenylethylamides by using Bischler-Napieralski conditions gave1-(5-chloro-2-nitrophenyl)-3,4- DHIQs (2a-c). Compounds 2a-c were then treated with SnCl2·2H2O in ethyl acetate to give 1-(5-chloro-2-aminophenyl)-3,4-DHIQs and 10-chloro-5,6- dihydroindazolo [3,2-a]isoquinolines (3a-c). Treatment of 1-(5-chloro-2-aminophenyl)-3,4-DHIQs with sodium borohydride in methanol gave 1-(5-chloro 2-aminophenyl)-1,2,3,4-THIQs (4a-c) in good yields. By treating all the THIQs with K2PtCl4 afforded their cis-dichloridoplatinum (II) complexes (5a-c). Three dichloroplatinums have been synthesized and the antitumor activity of these compounds was examined against four different human tumor cell lines. All of these compounds exhibited activity against MCF-7 cell line and showed good activity against WiDr cell line. The study then tests and evaluates antibiotic activities of fifteen synthetic drugs with DISK test method; the test result