A one-pot synthesis and biological activity of ageladine A and analogues

Sudhir R. Shengule, Wendy L. Loa-Kum-Cheung, Christopher R. Parish, Mélina Blairvacq, Laurent Meijer, Yoichi Nakao, Peter Karuso

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

LanguageEnglish
Pages2492-2503
Number of pages12
JournalJournal of Medicinal Chemistry
Volume54
Issue number7
DOIs
Publication statusPublished - 14 Apr 2011

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Metalloproteases
Phosphotransferases
Structure-Activity Relationship
Biological Products
Aldehydes
Cell Line
Ageladine A

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Shengule, S. R., Loa-Kum-Cheung, W. L., Parish, C. R., Blairvacq, M., Meijer, L., Nakao, Y., & Karuso, P. (2011). A one-pot synthesis and biological activity of ageladine A and analogues. Journal of Medicinal Chemistry, 54(7), 2492-2503. https://doi.org/10.1021/jm200039m
Shengule, Sudhir R. ; Loa-Kum-Cheung, Wendy L. ; Parish, Christopher R. ; Blairvacq, Mélina ; Meijer, Laurent ; Nakao, Yoichi ; Karuso, Peter. / A one-pot synthesis and biological activity of ageladine A and analogues. In: Journal of Medicinal Chemistry. 2011 ; Vol. 54, No. 7. pp. 2492-2503.
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Shengule, SR, Loa-Kum-Cheung, WL, Parish, CR, Blairvacq, M, Meijer, L, Nakao, Y & Karuso, P 2011, 'A one-pot synthesis and biological activity of ageladine A and analogues', Journal of Medicinal Chemistry, vol. 54, no. 7, pp. 2492-2503. https://doi.org/10.1021/jm200039m

A one-pot synthesis and biological activity of ageladine A and analogues. / Shengule, Sudhir R.; Loa-Kum-Cheung, Wendy L.; Parish, Christopher R.; Blairvacq, Mélina; Meijer, Laurent; Nakao, Yoichi; Karuso, Peter.

In: Journal of Medicinal Chemistry, Vol. 54, No. 7, 14.04.2011, p. 2492-2503.

Research output: Contribution to journalArticleResearchpeer-review

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Shengule SR, Loa-Kum-Cheung WL, Parish CR, Blairvacq M, Meijer L, Nakao Y et al. A one-pot synthesis and biological activity of ageladine A and analogues. Journal of Medicinal Chemistry. 2011 Apr 14;54(7):2492-2503. https://doi.org/10.1021/jm200039m