Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

E. Dolušić; P. Larrieu; C. Meinguet; D. Colette; A. Rives; S. Blanc; T. Ferain; L. Pilotte; V. Stroobant; J. Wouters; B. Van Den Eynde; B. Masereel; E. Delfourne; R. Frédérick

doi:10.1016/j.bmcl.2012.11.036

Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

E. Dolušić, P. Larrieu, C. Meinguet, D. Colette, A. Rives, S. Blanc, T. Ferain, L. Pilotte, V. Stroobant, J. Wouters, B. Van Den Eynde, B. Masereel, E. Delfourne, R. Frédérick

Research output: Contribution to journal › Article › peer-review

3 Downloads (Pure)

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 & Medicinal Chemistry Letters
Volume	23
Issue number	1
Early online date	24 Nov 2012
DOIs	https://doi.org/10.1016/j.bmcl.2012.11.036
Publication status	Published - 1 Jan 2013
Event	JFB 2011. - Liege, Belgium Duration: 19 May 2011 → …

Keywords

Cancer immunology
Indoleamine 2,3-dioxygenase
Molecular modeling
Pyrroloiminoquinones
Tsitsikammamines

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bmcl.2012.11.036

http://www.sciencedirect.com/science/article/pii/S0960894X12014795

Cite this

Dolušić, E., Larrieu, P., Meinguet, C., Colette, D., Rives, A., Blanc, S., Ferain, T., Pilotte, L., Stroobant, V., Wouters, J., Van Den Eynde, B., Masereel, B., Delfourne, E., & Frédérick, R. (2013). Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A. Bioorganic & Medicinal Chemistry Letters, 23(1), 47-54. https://doi.org/10.1016/j.bmcl.2012.11.036

@article{30e281aa469a4ad8bc6b8912ae5bd692,

title = "Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A",

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 = "Cancer immunology, Indoleamine 2,3-dioxygenase, Molecular modeling, Pyrroloiminoquinones, Tsitsikammamines",

author = "E. Dolu{\v s}i{\'c} and P. Larrieu and C. Meinguet and D. Colette and A. Rives and S. Blanc and T. Ferain and L. Pilotte and V. Stroobant and J. Wouters and {Van Den Eynde}, B. and B. Masereel and E. Delfourne and R. Fr{\'e}d{\'e}rick",

year = "2013",

month = jan,

day = "1",

doi = "10.1016/j.bmcl.2012.11.036",

language = "English",

volume = "23",

pages = "47--54",

journal = "Bioorganic & Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier",

number = "1",

note = "JFB 2011. ; Conference date: 19-05-2011",

}

Dolušić, E, Larrieu, P, Meinguet, C, Colette, D, Rives, A, Blanc, S, Ferain, T, Pilotte, L, Stroobant, V, Wouters, J, Van Den Eynde, B, Masereel, B, Delfourne, E & Frédérick, R 2013, 'Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A', Bioorganic & Medicinal Chemistry Letters, vol. 23, no. 1, pp. 47-54. https://doi.org/10.1016/j.bmcl.2012.11.036

TY - JOUR

T1 - Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

AU - Dolušić, E.

AU - Larrieu, P.

AU - Meinguet, C.

AU - Colette, D.

AU - Rives, A.

AU - Blanc, S.

AU - Ferain, T.

AU - Pilotte, L.

AU - Stroobant, V.

AU - Wouters, J.

AU - Van Den Eynde, B.

AU - Masereel, B.

AU - Delfourne, E.

AU - Frédérick, R.

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

UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84871024705&partnerID=MN8TOARS

U2 - 10.1016/j.bmcl.2012.11.036

DO - 10.1016/j.bmcl.2012.11.036

M3 - Article

C2 - 23218716

AN - SCOPUS:84871024705

SN - 0960-894X

VL - 23

SP - 47

EP - 54

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 1

T2 - JFB 2011.

Y2 - 19 May 2011

ER -

Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Embargoed Document

Fingerprint

Indoleamine 2,3-dioxygenase inhibitors: a patent review (2008-2012)

Discovery and preliminary SARs of keto-indoles as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors

CANTOL: Design and synthesis of indolamine dioxygenase (IDO) for the treatment of cancer

Physical Chemistry and characterization(PC2)

47th RICT: Drug Discovery and Selection.

JFB 2011.

XVIIIeme JOURNEE JEUNES CHERCHEURS

Cite this

Indoleamine 2,3-Dioxygenase Inhibitory Activity of Derivatives of Marine Alkaloid Tsitsikammamine A

Abstract

Keywords

UN SDGs

Access to Document

Other files and links

Embargoed Document

Fingerprint

Research output

Projects

Equipment

Activities

Cite this