合成茚[1,2-c]喹啉類衍生物為抗結核菌試劑

Synthesis of Indeno[1,2-c]quinoline Derivatives as Antituberculosis Agents

吳政炘(Cheng-Hsin Wu)

指導教授 ： 曾誠齊

共同指導教授 ： 陳義龍(Yeh-Long Chen)

高雄醫學大學/生命科學院/醫藥暨應用化學研究所/碩士(2012年)

https://doi.org/10.6832/KMU.2012.00023

摘要

第一線目前用於治療結核病（TB）感染的藥物有streptomycin，isoniazid (INH)，ethambutol，pyrazinamide，rifampicin。然而，目前的結核病治療方案，雖然高效，但還是不夠理想。近來，出現多重耐藥性（MDR）菌株和全球性的人類免疫缺陷病毒（HIV）的流行創造了結核分枝桿菌感染的替代藥物治療的迫切需要。在過去的幾年中，我們一直特別感興趣的如茚[1,2-c]喹啉，吲哚[2,3-b]喹啉，苯并呋喃[2,3-b]喹啉衍生物的合成被用來抗結核和抗癌的活性評估。
本論文介紹了合成一些茚[1,2-c]喹啉衍生物對於抗結核菌進行活性評估。其中，化合物40c表現出了最低抑菌濃度（MIC）<0.5?慊/mL比一線藥物INH（MIC = 0.8 - 1.2?慊/mL）更要優越。化合物40c屬於一種新型的結構，另外被發現不會抑制Vero細胞的生長，因此，很有潛力可以作為一種新型抗結核病藥物。

關鍵字

抗結核菌

並列摘要

The first-line drugs currently used for the treatment of tuberculosis (TB) infection are streptomycin, isoniazid (INH), ethambutol, pyrazinamide, and rifampicin. However, the current TB treatment regimens, although highly effective, are far from ideal. Recently, the emergence of multi-drug resistant (MDR) strains and the global human immunodeficiency virus (HIV) pandemic have created an urgent need for alternative drug treatments for Mycobacterium tuberculosis infection. Over the past few years, we have been particularly interested in the synthesis of condensed quinolines such as indeno[1,2-c]quinoline, indolo[2,3-b]quinoline, and benzofuro[2,3-b]quinoline derivatives for anti-TB and anticancer evaluations.
This thesis describes synthesis of certain indeno[1,2-c]quinoline derivatives for anti-TB evaluations. Among them, compound 40c exhibited a minimum inhibitory concentration (MIC) of < 0.5 ?慊/mL which was more active the positive INH (MIC = 0.8 - 1.2 μg/mL). Compound 40c belongs to a novel structure type and was not cytotoxic against the growth of Vero cells and therefore, could serve as a potential lead for the development of novel anti-TB drug candidate.

並列關鍵字

Antituberculosis

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