title: Synthesis and Biological Evaluation of New (-)-Englerin Analogues.
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).
authors.affiliation: Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain.
authors.forename: Laura
authors.identifier: 0000-0002-8750-2294
authors.initials: L
authors.lastname: López-Suárez
authors.affiliation: Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain.|Institute of Polymer Science and Technology, ICTP-CSIC, Juan de la Cierva 3, 28006, Madrid, Spain.
authors.forename: Lorena
authors.identifier: 0000-0002-4389-6113
authors.initials: L
authors.lastname: Riesgo
authors.affiliation: Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain.
authors.forename: Fernando
authors.identifier: 0000-0001-5377-9829
authors.initials: F
authors.lastname: Bravo
authors.affiliation: Molecular Targets Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA.
authors.forename: Tanya T
authors.initials: TT
authors.lastname: Ransom
authors.affiliation: Molecular Targets Laboratory, Molecular Discovery Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, 21702, USA. beutlerj@mail.nih.gov.
authors.forename: John A
authors.identifier: 0000-0002-4646-1924
authors.initials: JA
authors.lastname: Beutler
authors.affiliation: Institute of Chemical Research of Catalonia (ICIQ), Av. Països Catalans 16, 43007, Tarragona, Spain. aechavarren@iciq.es.|Departament de Química Analítica i Química Orgánica, Universitat Rovira i Virgili, C/Marcel⋅li Domingo s/n, 43007, Tarragona, Spain. aechavarren@iciq.es.
authors.forename: Antonio M
authors.identifier: 0000-0001-6808-3007
authors.initials: AM
authors.lastname: Echavarren
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D061565:Cycloaddition Reaction; D004354:Drug Screening Assays, Antitumor; D006046:Gold / Q000737:chemistry; D006801:Humans; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045789:Sesquiterpenes, Guaiane; C534971:englerin A; D006046:Gold
keywords: enantioselective synthesis; englerin A; gold catalysis; natural products; renal cancer; tumor growth inhibition