新穎脫氫硫胺[2,3-c]喹啉-12-酮衍生物、其製備方法及其應用THIOCHROMENO[2,3-C]QUINOLIN-12-ONE DERIVATIVES, PREPARATION METHOD AND APPLICATION THEREOF

專利類型

發明

專利國別 (專利申請國家)

美國

專利申請案號

14/180,707

專利證號

US 8,927,717 B1

專利獲證名稱

新穎脫氫硫胺[2,3-c]喹啉-12-酮衍生物、其製備方法及其應用THIOCHROMENO[2,3-C]QUINOLIN-12-ONE DERIVATIVES, PREPARATION METHOD AND APPLICATION THEREOF

專利所屬機關 (申請機關)

國防醫學院

獲證日期

2015/01/06

技術說明

一系列新穎thiochromeno[2,3-c]quinolin-12-one衍生物被合成出來並測試抗癌效果。於是合成50個具有四個平面環的結構並將不同的取代基團整合進來取代在C-6位置上，例如氨基、氧基和硫醇基。利用MTT試驗，測試其抑制PC-3與DU-145細胞株毒殺效果與topoisomerase drug screening實驗測試其相較於camptothecin與etoposide抑制其topoisomerase活性，發現有18個藥物的IC50 < 10 uM，另外拓譜酶的效果方面，也發現3個對於topoisomerase I跟II都有效果的藥物。此外，還有送交美國癌症研究中心測試60種不同癌症類型細胞株的體外細胞抗癌活性，總共選中的21個化合物於單一劑量10 μM下，其中A-2、A-7與A-14的mean GI% 分別為65.97, -11.06與 -51.89，進一步被選為5個劑量的進階實驗。雖然我們對此類化合物具毒殺癌症細胞、抑制拓樸異構酶的藥效機轉仍未完全了解，但這些衍生物仍然擁有明顯抑制癌細胞生長的能力、抑制拓樸異構酶的活性。本篇論文的研究目的即在合成新穎且有效的小分子化合物，以期對癌症治療藥物的發展上有所幫助。 A series of thiochromeno[2,3-c]quinolin-12-ones had been found to be potential DNA topoisomerase I inhibition drugs. The obtained compounds were evaluated by MTT assay, topoisomerase I and II drug screening, and also evaluated for their in vitro antitumor activity through the NCI 60 cell lines panel assay. Results of NCI selected 21 compounds showed that A-2, A-7 and A-14 had potent anticancer activity (mean GI% = 65.97, -11.06 and -51.89, respectively) under one-dose (10 μM ) screening, and they were selected for further experimentation, utilizing a five-dose level screening. Although the exact pharmaceutical mechanisms of synthesized compounds are not well known, these derivatives still possess obvious cytotoxicity effects on cancerous cell lines, as well as inhibition of topoisomerase activity. The purpose of this research is to synthesize novel and effective small molecular compounds and to evaluate their biological effect on antitumor activity for future drug development.

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