1,3-Benzothiazinone衍生物之合成及細胞保護作用之活性評估

神經退化性疾病包括 Alzheimer's Disease、Parkinson's Disease，另外，物理性造成之神經傷害，例如缺血性神經傷害(Ischemia/Stroke) 或頭部劇烈撞擊都是常見之神經傷害疾病。而研究指出，這些傷害會因為神經細胞中之膠質細胞如星狀細胞的維持而具有被保護之作用，相反的疾病造成之星狀細胞受損或凋亡，皆會進一步造成神經細胞之保護喪失而造成神經細胞之傷害甚至凋亡反應之發生，並可能為神經退化性疾病之重要機轉之一。因此保護星狀細胞可能具有保護神經細胞之作用。在眾多研究中發現，上述之傷害皆與 Ceramide 具有關連性，因此本實驗利用易於穿透細胞膜之 C2-ceramide 作為模擬星狀細胞(C6 glioma)因疾病或外力傷害而凋亡之過程，並以此作為藥物篩選之工具，評估合成化合物對於細胞保護之作用。 1,3-Benzothiazinone 衍生物在細胞毒性評估時發現具有細胞數量增加之現象，並且於正常細胞中不具有明顯毒性之特性，再加上關於抑制凋亡活性作用之報導，因此將這類衍生物作為評估細胞保護作用之化合物。其中發現，compound 5 在 5 及 10 μM下具有微弱的dose-dependent 的保護作用趨勢，但當濃度提高至 20μM以上即產生毒性作用，由結果推測compound 5 確實具有細胞保護之作用。如果藉由compound 5 作為 lead compound 並設法去除其毒性作用，可能有機會發展成為具有細胞保護功能之藥物。

關鍵字

細胞保護；神經膠質瘤；星狀細胞

並列摘要

Neurodegenerative diseases such as Alzheimer’s Disease, Parkinson’s Disease, and Stroke are common diseases of neuronal damage. It has been reported that these kind of damage might be protected by the maintance of astrocytes. On the contrary, diseases caused astrocyte damage or apoptosis would result in it’s loss in neuro- protective activities, even cause neuron damage and cell apoptosis. Which could be one of the mechanisms of neurodegenerative diseases. As a result, astrocytes protection might be a route for neuroprotection. Many researches have been reported that such damage is related to ceramide. As a result, we use C2-ceramide to induce apoptotic effect in C6-glioma, the astrocyte like cell line, to mimic the apoptotic condition in neurodegenerative disease and use it as a drug screening model to evaluate the cell protective activities of our compounds. During the cytotoxic evaluation of 1,3-benzothiazinone derivatives, we found that there is a increased cell number phenomena, their nearly no toxic character in the normal cell line, and reported antiapoptotic effect, which prompt us to evaluate if these compounds have cell protective activities We found that compound 5 in 5 and 10μM seems to have minor dose-dependent trend of cell protective activities, but the toxicity become profound when the concentration doubled. The results showed that compound 5 actually have cell protective activity Use compound 5 as a lead compound to reduce it’s toxicity might be a route for the development of cell protective agents.

並列關鍵字

Cell protection；C6 glioma；C2-Ceramide；1,3-Benzothiazinone

參考文獻

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1,3-Benzothiazinone衍生物之合成及細胞保護作用之活性評估

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