2,4,5-Trihydroxybenzaldehyde與Carpacin之合成及其活性之探討

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 博碩士論文 > Item 310902500/1016

jsp.display-item.identifier=請使用永久網址來引用或連結此文件: https://ir.csmu.edu.tw:8080/ir/handle/310902500/1016

题名:	2,4,5-Trihydroxybenzaldehyde與Carpacin之合成及其活性之探討 Total synthesis of 2,4,5-trihydroxybenzaldehyde and carpacin and study on their biological activity
作者:	鄭彥敏 Yang Ming Cheng
贡献者:	中山醫學院：生物化學研究所;曾翠華;李衍彰
关键词:	有機合成;2;4;5-trihydroxybenzaldehyde;抗血癌活性;Crapacin;抑制基因合成;GST活性;毒性 2;4;5-trihydroxybenzaldehyde;MTT;anticancer activity;HL-60;Carpacin;inhibite DNA synthesis;induce GST activity;toxic
日期:	1998
上传时间:	2010-04-01T06:39:49Z (UTC)
摘要:	我們合成出之2,4,5-trihydroxybenzaldehyde (2,4,5-THBA)為phenolic compound與由植物中萃取之具有良好抗氧化效果的phenolic protocatechuic acid的結構很像。也與具有抗腫瘤活性之catecholamine的結構很類似。因2,4,5-THBA兼具有2,5-dihydroxybenzaldehyde(2,5-DHBA)與3,4-dihydroxybenzaldehyde(3,4-DHBA)的化學結構,所以我們對其作活性測試。其對自由基(DPPH)有捕捉能力,具有抗氧化效果。以2,5-DHBA效果最強, 3,4-DHBA次之, 2,4,5-THBA最弱。3,4-DHBA及2,4,5-THBA對鼠肝細胞不具毒性,但2,5-DHBA則有毒性。關於抑制t-BHP誘發的鼠肝毒性及 lipid oxidation以2,5-DHBA作用最強, 2,4,5-THBA次之, 3,4-DHBA最弱。2,4,5-THBA對人類口腔黏膜纖維癌細(Kb cell),及人類肝癌細胞(HepG2 cell)毒性不強,但對人類血癌細胞(HL-60 cell)則有很強毒性比2,5-DHBA及3,4-DHBA還強。在合成過程中,我們也製備了natural product Carpacin。它可由Carpano樹的樹皮萃取出被當作鎮靜及安眠藥。也曾被合成出來當殺蟲劑。其類似物α與β-Asarone對鼠肝細胞具有基因毒性及其異構物myristicin對鼠肝細胞並無基因毒性,且可誘發出glutathion S-transferase(GST)等解毒酵素的活性。因並無文獻提出有關於Carpacin之活性報告,因此我們對其作活性測試。Carpacin對鼠肝細胞,老鼠肺細胞(V79),老鼠胚胎纖維母細胞(C3H10T1/2)及人類口腔黏膜纖維母細胞(BF)處理0.5 mM以上的濃度時皆有細胞毒性。Carpacin以0.5 mM以上的濃度處理鼠肝細胞,以MTT法測定細胞會大量死亡,以LDH酵素法測定LDH酵素會大量漏失,兩種測法互相符合。Carpacin在鼠肝細胞中會抑制DNA合成,在無毒劑量下可對鼠肝細胞誘發出GST活性。鼠肝細胞在處理Carpacin時,隨著Carpacin濃度上升GSH/GSSG的比例值隨之下降。其在1 mM時仍無捕捉自由基(DPPH)的能力,即無抗氧化能力。 We synthesis a compound, 2,4,5-trihydroxybenzaldehyde (2,4,5-THBA) which is a phenolic compound. It is similar in structure to phenolic protocatechuic acid that has wonderful antioxidation effect and is extracted from plant. 2,4,5-THBA is also similar in structure to catecholamine that has antitumor activity. 2,4,5-THBA possess both chemical structure of 2,5-dihydroxybenzaldehyde (2,5-DHBA) and 3,4-dihydroxybenzaldehyde (3,4-DHBA). So that we test all of their biological activity. They have ability to capture 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) and 2,5-DHBA is the best one. 3,4-DHBA is next to 2,5-DHBA and 2,4,5-THBA is the weakest. 3,4-DHBA and 2,4,5-THBA are not toxic to rat hepatocytes but 2,5-DHBA does. They can inhibit the tert-butyl hydroperoxide (t-BHP)-induced hepatoxicity and lipid oxidation. 2,5-DHBA has the best efficiency, 2,4,5-THBA is secondary and 3,4-DHBA is the weakest. 2,4,5-THBA is little toxic to human oral fibroblast cancer cell (KB cell) and human liver cancer cell (HepG2 cell). But it is very toxic to human leukemia cancer cell (HL-60 cell) and is stronger then 2,5-DHBA and 3,4-DHBA. In the synthesis we also get a intermediate, carpacin that is a natural product. It is extracted from the bark of Carpano tree and used in folk medicine like sedative. It has been synthesized as a possible insecticide, too. It is similar in structure to αandβ-Asarone that are genetoxic to rat hepatocytes. Carpacin''s isomer, myristicin is not genetoxic to rat hepatocytes and can induce glutathion S-transferase (GST) activity that is reported to have effect in rat hepatocytes. No literature reports the biological activity of carpacin. So that we do it. Carpacin is toxic to rat hepatocytes, mouse lung cell (V79 cell), mouth embryo fibroblast (C3H10T1/2 cell) and human oral fibroblast (BF cell) at above 0.5 mM. Most cells die and LDH leakage is much when rat hepatocytes are treated with carpacin at above 0.5 mM. Carpacin can inhibit DNA synthesis and induce GST activity at no toxic doses in rat hepatocytes. The ratio of GSH/GSSG is down in rat hepatocytes when the cells treated with carpacin followed the dose is up. It has no antioxidation effect that capture little 1,1-Diphenyl-2-picrylhydrazyl radical (DPPH) until at 1 mM.
URI:	http://140.128.138.153:8080/handle/310902500/1016
显示于类别:	[生化微生物免疫研究所] 博碩士論文

文件中的档案:

没有与此文件相关的档案.

在CSMUIR中所有的数据项都受到原著作权保护.

TAIR相关文章

数据加载中.....