合成具有生物活性黃嘌呤類的水溶性碳六十衍生物，並探討其抗發炎效果

Synthesis and Anti-inflammation evaluation of new water soluble fulleropyrrolidines bearing biologically active xanthine

廖健勝(Jian-Sheng Liao)

指導教授 ： 黃聲東

國立臺北科技大學/工程學院/生物科技研究所/碩士(2007年)

摘要

在最近的研究中發現，碳六十衍生物具有很廣泛的生物活性的應用，包括在抑制HIV蛋白酶、光動力療法、神經保護、選擇性核苷酸切割及吸收自由基等，但是由於碳六十在近代才被發現，所以碳六十衍生物在生物活性探討上還是不很多，尤其在碳六十衍生物對於抗發炎的研究上，更是少見。因此我們希望探討碳六十衍生物在抗發炎上的功效，於是我們合成了全新的具有黃嘌呤類的水溶性碳六十衍生物，當作抗發炎藥物，探討其是否有抗發炎功效。我們合成水溶性碳六十衍生物的方法是經由1-3 dipolar cycloaddition反應而成，而合成出的黃嘌呤類水溶性碳六十衍生物1a與1b，在1％的DMSO純水下，其溶解度可達10μM左右，且經由UV-visible spectra實驗，證明碳六十衍生物1a與1b具有水溶性，之後我們再藉由刺激巨噬細胞釋放細胞激素，來探討NO與TNF-α被碳六十衍生物抑制的效果。最後在我們的研究中發現，當巨噬細胞經由LPS刺激下，加入所合成的碳六十衍生物1b (10μM)，有助於大幅降低NO與TNF-α的產生，達到抗發炎的功效。而我們相信我們找到了一個新的設計抗發炎藥物的方向，來降低當發炎時所產生的NO與TNF-α，在往後我們也將會合成另一系列的抗發炎水溶性碳六十衍生物，呈現給大家與大家分享。

關鍵字

碳六十 ； 抗發炎 ； 黃嘌呤

並列摘要

Research in the filed of water soluble C60 fullerene derivatives has significantly increase due to a broad range of biological activity that was found for these compounds. The biological applications have included studies on the inhibition of HIV-protease, photodynamic therapy, neuroprotection, and site-selective DNA cleavage.We are interested in prepare a new classed of water soluble fullerene hybrids bearing a xanthine analogues as new anti-inflammation agents and evaluate their effects on the concentration of NO and TNF-α produced by the activated macrophages. The water soluble fulleropyrrolidines bearing biologically active xanthine were prepared via 1-3 dipolar cycloaddition. Their maximum solubility in 1% DMSO aqueous media were in rang of ~10μM.Our preliminary biological evaluation using cell linage to simulate the type of macrophages during inflammation had identified that 10μM of fulleropyrrolidines was effective to reduce the concentration of NO and TNF-α.We believe that the present study describe a new approach toward designing agents which possess the ability to reduce the concentration of both NO and TNF-α during inflammation, and we believed that this new approach holds promise for providing the development of new generation of the potent anti-inflammation agent.

並列關鍵字

Fullerene ； Anti-inflammation ； xanthine

參考文獻

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