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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 Isoquinolina Alkaloids Marine natural products Heterocyclic compounds Antineoplastic agents Isoquinoline |
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: http://dx.doi.org/10.1021/jm0602458 |
It is part of: | Journal of Medicinal Chemistry, 2006, vol. 49, num. 11, p. 3257-3268 |
URI: | http://hdl.handle.net/2445/56314 |
Related resource: | http://dx.doi.org/10.1021/jm0602458 |
ISSN: | 0022-2623 |
Appears in Collections: | Articles publicats en revistes (Farmacologia, Toxicologia i Química Terapèutica) Articles publicats en revistes (Química Inorgànica i Orgànica) |
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