Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

Pierre Vandurm; Christine Cauvin; Allan Guiguen; Benoît Georges; Kiet Le Van; Valérie Martinelli; Christelle Cardona; Gladys Mbemba; Jean François Mouscadet; László Hevesi; Carine Van Lint; Johan Wouters

doi:10.1016/j.bmcl.2009.06.044

Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

Pierre Vandurm, Christine Cauvin, Allan Guiguen, Benoît Georges, Kiet Le Van, Valérie Martinelli, Christelle Cardona, Gladys Mbemba, Jean François Mouscadet, László Hevesi, Carine Van Lint, Johan Wouters

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

Abstract

Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

Original language	English
Pages (from-to)	4806-4809
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	19
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2009.06.044
Publication status	Published - 15 Aug 2009

Keywords

β-Diketo
HIV-1
Integrase inhibitors
Quinolinone

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10.1016/j.bmcl.2009.06.044

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CCDC 730039: Experimental Crystal Structure Determination
Vandurm, P. (Contributor), Cauvin, C. (Contributor), Guiguen, A. (Contributor), Georges, B. (Contributor), Le Van, K. (Contributor), Martinelli, V. (Contributor), Cardona, C. (Contributor), Mbemba, G. (Contributor), Mouscadet, J. (Contributor), HEVESI, L. (Contributor), Le Van, K. (Contributor) & WOUTERS, J. (Contributor), Cambridge Crystallographic Data Centre, 1 Jan 2010
DOI: 10.5517/ccshnnk, http://www.ccdc.cam.ac.uk/services/structure_request?id=doi:10.5517/ccshnnk&sid=DataCite
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Vandurm, P., Cauvin, C., Guiguen, A., Georges, B., Van, K. L., Martinelli, V., Cardona, C., Mbemba, G., Mouscadet, J. F., Hevesi, L., Lint, C. V., & Wouters, J. (2009). Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor. Bioorganic & Medicinal Chemistry Letters, 19(16), 4806-4809. https://doi.org/10.1016/j.bmcl.2009.06.044

Vandurm, Pierre ; Cauvin, Christine ; Guiguen, Allan ; Georges, Benoît ; Van, Kiet Le ; Martinelli, Valérie ; Cardona, Christelle ; Mbemba, Gladys ; Mouscadet, Jean François ; Hevesi, László ; Lint, Carine Van ; Wouters, Johan. / Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor. In: Bioorganic & Medicinal Chemistry Letters. 2009 ; Vol. 19, No. 16. pp. 4806-4809.

@article{ff5790f799e849b58e8db77cddd5f55d,

title = "Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-buteno{\"i}c acid as HIV-1 integrase inhibitor",

abstract = "Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-buteno{\"i}c acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.",

keywords = "β-Diketo, HIV-1, Integrase inhibitors, Quinolinone",

author = "Pierre Vandurm and Christine Cauvin and Allan Guiguen and Beno{\^i}t Georges and Van, {Kiet Le} and Val{\'e}rie Martinelli and Christelle Cardona and Gladys Mbemba and Mouscadet, {Jean Fran{\c c}ois} and L{\'a}szl{\'o} Hevesi and Lint, {Carine Van} and Johan Wouters",

year = "2009",

month = aug,

day = "15",

doi = "10.1016/j.bmcl.2009.06.044",

language = "English",

volume = "19",

pages = "4806--4809",

journal = "Bioorganic and medicinal chemistry letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "16",

}

Vandurm, P, Cauvin, C, Guiguen, A, Georges, B, Van, KL, Martinelli, V, Cardona, C, Mbemba, G, Mouscadet, JF, Hevesi, L, Lint, CV & Wouters, J 2009, 'Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor', Bioorganic & Medicinal Chemistry Letters, vol. 19, no. 16, pp. 4806-4809. https://doi.org/10.1016/j.bmcl.2009.06.044

Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor. / Vandurm, Pierre; Cauvin, Christine; Guiguen, Allan; Georges, Benoît; Van, Kiet Le; Martinelli, Valérie; Cardona, Christelle; Mbemba, Gladys; Mouscadet, Jean François; Hevesi, László; Lint, Carine Van; Wouters, Johan.

In: Bioorganic & Medicinal Chemistry Letters, Vol. 19, No. 16, 15.08.2009, p. 4806-4809.

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

TY - JOUR

T1 - Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

AU - Vandurm, Pierre

AU - Cauvin, Christine

AU - Guiguen, Allan

AU - Georges, Benoît

AU - Van, Kiet Le

AU - Martinelli, Valérie

AU - Cardona, Christelle

AU - Mbemba, Gladys

AU - Mouscadet, Jean François

AU - Hevesi, László

AU - Lint, Carine Van

AU - Wouters, Johan

PY - 2009/8/15

Y1 - 2009/8/15

N2 - Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

AB - Ethyl [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl]-4-hydroxy-2-oxo-3-butenoate 1 and [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid 2 were synthesized as potential HIV-1 integrase inhibitors and evaluated for their enzymatic and antiviral activity, acidic compound 2 being more potent than ester compound 1. X-ray diffraction analyses and theoretical calculations show that the diketoacid chain of compound 2 is preferentially coplanar with the quinolinone ring (dihedral angle of 0-30°). Docking studies suggest binding modes in agreement with structure-activity relationships.

KW - β-Diketo

KW - HIV-1

KW - Integrase inhibitors

KW - Quinolinone

UR - http://www.scopus.com/inward/record.url?scp=67651091690&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2009.06.044

DO - 10.1016/j.bmcl.2009.06.044

M3 - Article

C2 - 19556126

AN - SCOPUS:67651091690

VL - 19

SP - 4806

EP - 4809

JO - Bioorganic and medicinal chemistry letters

JF - Bioorganic and medicinal chemistry letters

SN - 0960-894X

IS - 16

ER -

Structural and theoretical studies of [6-bromo-1-(4-fluorophenylmethyl)-4(1H)-quinolinon-3-yl)]-4-hydroxy-2-oxo-3-butenoïc acid as HIV-1 integrase inhibitor

Abstract

Keywords

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CCDC 730039: Experimental Crystal Structure Determination

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