Synthesis and structure-activity relationship study of potent cytotoxic analogues of the marine alkaloid lamellarin D
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The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogues of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-α]isoquinoline-3-carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB-231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data, the SAR study concluded that more than 75% of the open-chain Lam-D analogues tested showed cytotoxicity in a low micromolar GI 50 range.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Medicinal Chemistry |
Vol/bind | 49 |
Udgave nummer | 11 |
Sider (fra-til) | 3257-3268 |
Antal sider | 12 |
ISSN | 0022-2623 |
DOI | |
Status | Udgivet - 1 jun. 2006 |
ID: 240981261