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ChemMedChem. 2016 May 6;11(9):1003-7. doi: 10.1002/cmdc.201600040. Epub 2016 Mar 23.

Synthesis and Biological Evaluation of New (-)-Englerin Analogues.

Author information

1
Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain.
2
Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.
3
Molecular Targets Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.
4
Molecular Targets Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA. beutlerj@mail.nih.gov.
5
Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain. aechavarren@iciq.es.
6
Departament de Química Analítica i Química Orgánica, Universitat Rovira i Virgili, C/Marcel⋅li Domingo s/n, 43007, Tarragona, Spain. aechavarren@iciq.es.

Abstract

We report the synthesis and biological evaluation of a series of (-)-englerin A analogues obtained along our previously reported synthetic route based on a stereoselective gold(I) cycloaddition process. This synthetic route is a convenient platform to access analogues with broad structural diversity and has led us to the discovery of unprecedented and easier-to-synthesize derivatives with an unsaturation in the cyclopentyl ring between C4 and C5. We also introduce novel analogues in which the original isopropyl motif has been substituted with cyclohexyl, phenyl, and cyclopropyl moieties. The high selectivity and growth-inhibitory activity shown by these new derivatives in renal cancer cell lines opens new ways toward the final goal of finding effective drugs for the treatment of renal cell carcinoma (RCC).

KEYWORDS:

enantioselective synthesis; englerin A; gold catalysis; natural products; renal cancer; tumor growth inhibition

PMID:
27005578
PMCID:
PMC4926265
DOI:
10.1002/cmdc.201600040
[Indexed for MEDLINE]
Free PMC Article

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