Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D
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 scaffo...
| Authors: | ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2006 |
| Country: | España |
| Institution: | Universidad de Barcelona |
| Repository: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/56314 |
| Online Access: | https://hdl.handle.net/2445/56314 |
| Access Level: | Open access |
| Keyword: | Alcaloides Productes naturals marins Compostos heterocíclics Medicaments antineoplàstics Isoquinolina Alkaloids Marine natural products Heterocyclic compounds Antineoplastic agents Isoquinoline |
| Summary: | 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. |
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