Tsitsikammamines belonging to the pyrroloiminoquinone class of marine alkaloids were first isolated and characterized in 1996 from a Latrunculiidae sponge collected in the Tsitsikamma Marine Reserve of South Africa. These and related compounds have attracted attention due to various interesting biological properties, including cytotoxicity, topoisomerase inhibition, antimicrobial and antifungal activity. Recently, two novel regioisomeric series of tsitsikammamine A analogues were described. The products were evaluated in an in vitro antiproliferative test against several cancer and normal (fibroblast) cell lines. This work allowed identifying a cytotoxic synthetic intermediate 1 with an unknown mechanism of action.
Indoleamine 2,3-dioxygenase (IDO) was identified as an important factor in the tumor immune evasion mechanism. It was demonstrated that many human tumors express IDO in a constitutive manner. Our groups recently published several articles on the development of new series of IDO inhibitors. Here, we would like to report for the first time on an inhibitory activity of tsitsikammamine derivatives against IDO. Tsitsikammamine A analogue 2 displays submicromolar potency in an enzymatic test. A number of derivatives are also moderately active in a cellular test, establishing interest in this class of compounds as a potential source of leads for the development of new pharmaceutically useful IDO inhibitors.
|Title of host publication||Oral Communication, 25èmes Journées Franco-belges de Pharmacochimie, 19-20/05/11, Liège|
|Subtitle of host publication||De la conception à la réalisation en pharmacochimie|
|Number of pages||1|
|Publication status||Published - 2011|
|Event||JFB 2011. - Liege, Belgium|
Duration: 19 May 2011 → …
|Period||19/05/11 → …|