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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.

Original publication

DOI

10.1016/j.bmcl.2012.11.036

Type

Journal article

Journal

Bioorg Med Chem Lett

Publication Date

01/01/2013

Volume

23

Pages

47 - 54

Keywords

Alkaloids, Binding Sites, Cell Line, Cell Survival, Humans, Indoleamine-Pyrrole 2,3,-Dioxygenase, Molecular Docking Simulation, Protein Structure, Tertiary, Pyrroles, Quinolines, Structure-Activity Relationship