| Summary: | 博士 === 中國醫藥學院 === 藥物化學研究所 === 90 === 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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