Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10596107 | Bioorganic & Medicinal Chemistry Letters | 2013 | 8 Pages |
Abstract
Tsitsikammamines are marine alkaloids whose structure is based on the pyrroloiminoquinone scaffold. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial, antifungal and antimalarial activity.Indoleamine 2,3-dioxygenase (IDO1) is a well-established therapeutic target as an important factor in the tumor immune evasion mechanism. In this preliminary communication, we report the inhibitory activity of tsitsikammamine derivatives against IDO1. Tsitsikammamine A analogue 11b displays submicromolar potency in an enzymatic assay. A number of derivatives are also active in a cellular assay while showing little or no activity towards tryptophan 2,3-dioxygenase (TDO), a functionally related enzyme. This IDO1 inhibitory activity is rationalized by molecular modeling studies. An interest is thus established in this class of compounds as a potential source of lead compounds for the development of new pharmaceutically useful IDO1 inhibitors.
Keywords
IDO1NHDFTDOSARIMACHBSS(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideHanks balanced salt solutionMTTSDS–PAGEEDTAEthylenediaminetetraacetic acidSodium dodecyl sulfate polyacrylamide gel electrophoresisCancer immunologyindoleamine 2,3-dioxygenaseTryptophan 2,3-dioxygenaseStructure–activity relationshipsMolecular modelingimmobilized metal ion affinity chromatography
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Eduard DoluÅ¡iÄ, Pierre Larrieu, Céline Meinguet, Delphine Colette, Arnaud Rives, Sébastien Blanc, Thierry Ferain, Luc Pilotte, Vincent Stroobant, Johan Wouters, Benoît Van den Eynde, Bernard Masereel, Evelyne Delfourne, Raphaël Frédérick,