TY - JOUR
T1 - A one-pot synthesis and biological activity of ageladine A and analogues
AU - Shengule, Sudhir R.
AU - Loa-Kum-Cheung, Wendy L.
AU - Parish, Christopher R.
AU - Blairvacq, Mélina
AU - Meijer, Laurent
AU - Nakao, Yoichi
AU - Karuso, Peter
PY - 2011/4/14
Y1 - 2011/4/14
N2 - A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition to develop the first structure-activity relationship of ageladine A analogues. One compound, which showed significant kinase activity but little MMP inhibitory activity, was found to be highly active in an antiangiogenic screen, suggesting that the angiogenic activity of ageladine A is not associated with MMP inhibition but rather kinase inhibitory activity. Cytotoxicity was excluded as a mode of action by the assay of ageladine A and an analogue against 60 human cell lines.
AB - A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition to develop the first structure-activity relationship of ageladine A analogues. One compound, which showed significant kinase activity but little MMP inhibitory activity, was found to be highly active in an antiangiogenic screen, suggesting that the angiogenic activity of ageladine A is not associated with MMP inhibition but rather kinase inhibitory activity. Cytotoxicity was excluded as a mode of action by the assay of ageladine A and an analogue against 60 human cell lines.
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U2 - 10.1021/jm200039m
DO - 10.1021/jm200039m
M3 - Article
C2 - 21413800
AN - SCOPUS:79953767989
SN - 0022-2623
VL - 54
SP - 2492
EP - 2503
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
IS - 7
ER -