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Title: Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
Author: Pla Queral, Daniel
Marchal, Antonio
Olsen, Christian A.
Francesch, Andrés
Cuevas, Carmen
Albericio Palomera, Fernando
Álvarez Domingo, Mercedes
Keywords: Alcaloides
Productes naturals marins
Compostos heterocíclics
Medicaments antineoplàstics
Marine natural products
Heterocyclic compounds
Antineoplastic agents
Issue Date: 6-May-2006
Publisher: American Chemical Society
Abstract: 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 analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]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 analogs tested showed cytotoxicity in a low micromolar GI50 range.
Note: Versió postprint del document publicat a:
It is part of: Journal of Medicinal Chemistry, 2006, vol. 49, num. 11, p. 3257-3268
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ISSN: 0022-2623
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)
Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica)

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