4-苯胺喹啉-3-羧酸衍生物的合成與生物活性

中文摘要喹啉之取代衍生物具有非常廣泛之生物活性，如抗癌、抗菌、殺黴菌、抗發炎等，尚具有止痛的功效，因此醫藥化學家為了探討此一系列結構與活性之間關聯性，積極合成新的Quinoline衍生物，期望此類雜環化合物，可抑制Src酪氨酸蛋白質激酶活性而製成抗癌製劑。為了研究此一系列結構與活性之間的關聯性，我們合成出一系列-4-苯胺喹啉在碳-6、碳-8位置有氟和在碳-7位置含有piperazine等新的雜環類化合物,且探討此一系列化合物的生物活性。初步的抗癌活性分析結果顯示，在這些化合物中大部份的化合物對於肺癌細胞（NCI-G460）、.乳癌細胞（MCF7）、中樞神經癌細胞（SF-268）的成長具抑制活性，其中以4-(4-乙醯苯胺基)-6,8-二氟-7-哌?-1-基-喹啉-3羧酸乙酯在100 μM濃度下，對肺癌細胞(NCI-H460)、乳癌細胞(MCF7)、中樞神經癌細胞(SF-268)更有100 %生長抑制之活性。此外也由4-苯胺喹啉合成出6-氟-4-[4-(1-羥基亞胺)苯基] -7-哌?-1-基-喹啉-3-羧酸乙酯類的化合物,並將介紹這一系列衍生化合物的初步生物活性的探討。

關鍵字

苯胺喹晽

並列摘要

Abstract The series of quinoline derivatives is a heterocycle which possessing a wide variety of biological activities, such as anticancer, bacteriocial, fungicidal, anti-inflammatory, and analgesic activities. In order to find out the relationships between activities and the structures of quinoline desivatives, The medicinal chemists has spent a great effort to synthesize these series of compound, Hoping that a special reagent can be discovered to inhibit the activity of Src protein kinase. and further connected to an anticancer agent. We synthesized 4-anilinoquinoline,with fluoro atom at C-6 and C-8 accompany with piperazine at C-7 position for the studies of Structure activity relationships(SAR). The preliminary anticancer assay that show these compound possessing the bioactivities against the growth of NCI-H460 (lung cancer), MCF7 (breast cancer), SF-268 (CNS cancer). 4-(4-Acetylphenylamino)—6,8-difluoro-7- piperazin-1-yl-quinoline-3-carboxylic acid ethyl ester was the most effective one, which has good growth inhibition properties toward NCI-H460,MCF7, and. SF-268 at concentration of 100μM. In addition,the tricyclic analogs of 6-fluroro-4-[4-(1-hydroxyimino-ethyl) phenylamino]-7-piperazin-1-yl-quinoline-3-carboxylic acid ethyl ester, had also been synthesized for anticancer evaluation.