KMID : 0043320010240050397
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Archives of Pharmacal Research 2001 Volume.24 No. 5 p.397 ~ p.401
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Anti-Angiogenic Activities of Gliotoxin and 1ts Methylthio-Derivative, Fungal Metabolites
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Lee Hee-Jung
Lee Jeong-Hyung Hwang Bang-Yeon Kim Hang-Sub Lee Jung-Joon
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Abstract
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In the search for new naturally occurring angiogenic inhibitory we found that culture broths from two unidentified fungal strains exerted potent inhibitory activities on capillary-like tube formation of human umbilical vein endothelial cells (HUVEC) in vitro. Two active compounds were isolated by bioassay-guided separation and their structures were identified as gliotoxin (1) and its derivative methylthiogliotoxin (2) by spectroscopic analyses. These compounds significantly inhibited the migration of HUVEC assessed by in vitro wounding migration assay and exhibited at least 10 times more potent inhibition of proliferation of HUVECs as compared with that of cancer cell lines such as HeLa, MCF-7, and KB 3-1 cells. Especially, gliotoxin having disulfide group exerted more potent activities than methylthiogliotoxin, suggesting that gliotoxin could be a useful compound for further study as an anti-angiogenic agent.
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KEYWORD
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Gliotoxin, Methylthiogliotoxin, Anti-angiogenic activity, HUVECs, Wound migration, Cytotoxicity
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