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.
| Original language | English |
|---|---|
| Pages (from-to) | 47-54 |
| Number of pages | 8 |
| Journal | Bioorganic and medicinal chemistry letters |
| Volume | 23 |
| Issue number | 1 |
| Early online date | 24 Nov 2012 |
| DOIs | |
| Publication status | Published - 1 Jan 2013 |
| Event | JFB 2011. - Liege, Belgium Duration: 19 May 2011 → … |
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Keywords
- Cancer immunology
- Indoleamine 2,3-dioxygenase
- Molecular modeling
- Pyrroloiminoquinones
- Tsitsikammamines
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Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. / Dolusic, Eduard; Larrieu, Pierre; Meinguet, Céline; Colette, Delphine; Rives, Arnaud; Blanc, Sébastien; Ferain, Thierry; Pilotte, Luc; Stroobant, Vincent; Wouters, Johan; Van den Eynde, Benoît; Masereel, Bernard; Delfourne, Evelyne; Frédérick, Raphaël.
In: Bioorganic and medicinal chemistry letters, Vol. 23, No. 1, 01.01.2013, p. 47-54.Research output: Contribution to journal › Article
TY - JOUR
T1 - Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A
AU - Dolusic, Eduard
AU - Larrieu, Pierre
AU - Meinguet, Céline
AU - Colette, Delphine
AU - Rives, Arnaud
AU - Blanc, Sébastien
AU - Ferain, Thierry
AU - Pilotte, Luc
AU - Stroobant, Vincent
AU - Wouters, Johan
AU - Van den Eynde, Benoît
AU - Masereel, Bernard
AU - Delfourne, Evelyne
AU - Frédérick, Raphaël
PY - 2013/1/1
Y1 - 2013/1/1
N2 - 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.
AB - 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.
KW - Cancer immunology
KW - Indoleamine 2,3-dioxygenase
KW - Molecular modeling
KW - Pyrroloiminoquinones
KW - Tsitsikammamines
U2 - 10.1016/j.bmcl.2012.11.036
DO - 10.1016/j.bmcl.2012.11.036
M3 - Article
C2 - 23218716
AN - SCOPUS:84871024705
VL - 23
SP - 47
EP - 54
JO - Bioorganic and medicinal chemistry letters
JF - Bioorganic and medicinal chemistry letters
SN - 0960-894X
IS - 1
ER -