1. Synthesis and Biological Evaluation of New (−)‐Englerin Analogues
- Author
-
John A. Beutler, Riesgo Lorena, Antonio M. Echavarren, Fernando Bravo, Tanya T. Ransom, Laura López-Suarez, Química Analítica i Química Orgànica, and Universitat Rovira i Virgili
- Subjects
EnglerinA ,Stereochemistry ,natural products ,Cell Survival ,renal cancer ,Structural diversity ,Stereoisomerism ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Catalysis ,Sesquiterpenes, Guaiane ,Structure-Activity Relationship ,Cell Line, Tumor ,Drug Discovery ,tumor growth inhibition ,Structure–activity relationship ,Humans ,enantioselective synthesis ,General Pharmacology, Toxicology and Pharmaceutics ,Biological evaluation ,Pharmacology ,Full Paper ,Cycloaddition Reaction ,1860-7179 ,010405 organic chemistry ,Chemistry ,Organic Chemistry ,Enantioselective synthesis ,englerin A ,Química ,Full Papers ,Combinatorial chemistry ,Antineoplastic Agents, Phytogenic ,Cycloaddition ,gold catalysis ,0104 chemical sciences ,3. Good health ,Or -- Catàlisi ,Molecular Medicine ,Stereoselectivity ,Gold ,Drug Screening Assays, Antitumor ,Isopropyl - 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).
- Published
- 2016
- Full Text
- View/download PDF