Pla Queral, DanielMarchal, AntonioOlsen, Christian A.Francesch, AndrésCuevas, CarmenAlbericio Palomera, FernandoÁlvarez Domingo, Mercedes2014-07-252014-07-252006-05-060022-2623https://hdl.handle.net/2445/56314The 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.12 p.application/pdfeng(c) American Chemical Society , 2006AlcaloidesProductes naturals marinsCompostos heterocíclicsMedicaments antineoplàsticsIsoquinolinaAlkaloidsMarine natural productsHeterocyclic compoundsAntineoplastic agentsIsoquinolineinfo:eu-repo/semantics/article5385802014-07-25info:eu-repo/semantics/openAccess