3,6,9-置換唑衍生物之合成與生理活性; Synthesis and Biological Activity of 3,6,9-Substituted Carbazole Derivatives

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Title:	3,6,9-置換唑衍生物之合成與生理活性;Synthesis and Biological Activity of 3,6,9-Substituted Carbazole Derivatives
Authors:	李春燕;Lee Chun-Yann
Contributors:	中國醫藥學院藥物化學研究所
Keywords:	抗血小板活性;抗發炎活性;嗜中性白血球脫顆粒反應;嗜中性白血球形成過氧自由基;小神經膠質細胞;人類血癌細胞株;細胞增殖抑制作用;carbazole;antiplatelet activity;anti-inflammatory;neutrophil degranulation;neutrophil superoxide formation;microglia cell;leukemia cell lines;antiproliferation
Date:	1991
Issue Date:	2009-12-03 10:03:01 (UTC+8)
Abstract:	中文摘要為了尋找新型生物活性物質，著者以9-benzylcarbazole-3-carbinol為先導化合物，合成了一系列衍生物，並評估其抗血小板活性、抗炎活性及小神經膠質細胞之抑制活性，建立了初步化學結構與各生理活性的關係。從本研究中發現化合物9-(o-chlorobenzyl)carbazole-3-carbaldehyde (3b)、9-(o-chlorobenzyl)carbazole-3-carbinol (4b)、9-(p-chlorobenzyl)carbazole-3- carbinol (4d)及9-benzylcarbazole-3-aldoxime (7)呈現顯著的抗血小板活性，而且其抑制形態類似YC-1。化合物3b同時對嗜中性白血球脫顆粒反應及嗜中性白血球形成過氧自由基呈現明顯的抑制活性，而化合物4b及4d只對嗜中性白血球脫顆粒反應呈現強力的抑制活性而已，其IC50均為2.0μM，相當於TFP 6~7倍的強度。化合物3b及4b被確認為新型的小神經膠質細胞活化之抑制劑，經作用機轉的探討結果，得知其作用機轉特異，為頗具潛力的前導化合物。9-(m- chlorobenzyl)carbazole-3-carbaldehyde (3c)，9-benzylcarbazole-3-carbinol (4a)及9-(m-chlorobenzyl)carbazole-3-carbinol (4c)，對HL 60、U 937及K 562等人類血癌細胞株之增殖呈現顯著的抑制活性。; Abstract In order to search for biological active compound, 9-benzyl carbazole-3-carbinol was used as a lead compound, and a series of its derivatives has been prepared. The antiplatelet, anti-inflammatory, inhibitory effect on microglia cells and human leukemia cells lines of these carbazole derivatives were evaluated. The structure-activity relationships in each system were also examined. 9-benzyl carbazole-3-carbaldehyde (3a), 9-(o-chlorobenzyl)carbazole-3-carbaldehyde (3b), 9-(o-chlorobenzyl)carbazole-3-carbinol (4b), 9-(p-chlorobenzyl)carbazole -3-carbinol (4d) and 9-benzylcarbazole-3-aldoxime (7) demonstrated significant antiplatelet activity. Their inhibitory profile is comparable to that of YC-1. Compound 3b showed simultaneously potent inhibition against neutrophil degranulation and neutrophil superoxide formation.Compound 4b and 4d demonstrated selective inhibition toward neutrophil degranulation with inhibitory potency (IC50 2.0 μM) equal about 6~7 times that of positive control TFP. Compounds 3b and 4b were identified as new class of inhibitors for microglia cell activation. Study of their action mechanism suggested that they act through unique mechanism and should be considered as novel lead compounds for further exploration. 9-(m-chlorobenzyl)carbazole-3- carbaldehyde (3c), 9-benzylcarbazole-3-carbinol (4a) and 9-(m-chlorobenzyl) carbazole-3-carbinol (4c) demonstrated significant antiproliferation against HL 60, U 937 and K 562 leukemia cell lines.
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