Journal articles
Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication
Karine Barral
1, 2
Clément Weck
2
Nadine Payrot
2
Loic Roux
2
Céline Durafour
3
Fabien Zoulim
4
Johan Neyts
5
Jan Balzarini
6, 5
Bruno Canard
7
Stephane Priet
7
Karine Alvarez
7
Karine Barral 1, 2
Author IdHAL : karine-barral ORCID : https://orcid.org/0000-0003-0842-1793
Clément Weck 2
Author
Nadine Payrot 2
Author
Loic Roux 2
Author
Bruno Canard 7
Author IdHAL : bruno-canard ORCID : https://orcid.org/0000-0003-4924-1991
Stephane Priet 7
Author
Karine Alvarez 7
Author IdHAL : karine-alvarez
1
CRCM / U891 Inserm - Centre de Recherche en Cancérologie de Marseille (France)
- Institut Paoli-Calmettes (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U891 (101, rue de Tolbiac, 75013 Paris - France)
- CNRS - Centre National de la Recherche Scientifique : UPR3081 (France)
2
AFMB - Architecture et fonction des Macromolécules Biologiques - UMR 6098 (Marseille - France)
- Université de Provence - Aix-Marseille 1 (3, place Victor Hugo - 13331 Marseille Cedex 03 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR6098 (France)
3
UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon (28, rue Laennec - 69373 Lyon - France)
- Centre Léon Bérard [Lyon] (28, rue Laennec 69373 LYON Cedex 08 - France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR5286 (France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U1052 (101, rue de Tolbiac, 75013 Paris - France)
4
Virus des hépatites et pathologies associées (Centre de Recherche Inserm 151, Cours Albert Thomas 69424 LYON CEDEX 03 - France)
- UCBL - Université Claude Bernard Lyon 1 (43, boulevard du 11 novembre 1918, 69622 Villeurbanne cedex - France)
- Université de Lyon (92 rue Pasteur - CS 30122, 69361 Lyon Cedex 07 - France)
- INSERM - Institut National de la Santé et de la Recherche Médicale : U271 (101, rue de Tolbiac, 75013 Paris - France)
5
Rega Institute for Medical Research [Leuven, België] (Minderbroedersstraat 10, B 3000 Leuven - Belgium)
- KU Leuven - Catholic University of Leuven - Katholieke Universiteit Leuven (Oude Markt 13 - bus 5005, 3000 Leuven - Belgium)
6
Laboratory of Medicinal Chemistry (Belgium)
- Rega Institute (France)
- Catholic University of Leuven (France)
7
AFMB - Architecture et fonction des macromolécules biologiques (Faculté des Sciences de Luminy - ESIL 163 avenue de Luminy CP 925 13288 MARSEILLE CEDEX 09 - France)
- CNRS - Centre National de la Recherche Scientifique : UMR7257 (France)
- AMU - Aix Marseille Université : UMR7257 (Aix-Marseille Université Jardins du Pharo 58 Boulevard Charles Livon 13284 Marseille cedex 7 - France)
- INRA - Institut National de la Recherche Agronomique : USC1408 (France)
Abstract : 9-[2-(Thiophosphonomethoxy)ethyl]adenine 3 and (R)-9-[2-(Thiophosphonomethoxy)propyl]adenine 4 were synthesized as the first thiophosphonate nucleosides bearing a sulfur atom at the α-position of the acyclic nucleoside phosphonates PMEA and PMPA. Thiophosphonates S-PMEA 3 and S-PMPA 4 were evaluated for in vitro activity against HIV-1 (subtypes A to G), HIV-2 and HBV-infected cells, and found to exhibit potent antiretroviral activity. We showed that their diphosphate forms S-PMEApp 5 and S-PMPApp 6 are readily incorporated by wild-type (WT) HIV-1 RT into DNA and act as DNA chain terminators. Compounds 3 and 4 were evaluated for in vitro activity against a broad panel of DNA and RNA viruses and displayed beside HIV a moderate activity against herpes simplex virus and vaccinia viruses. In order to measure enzymatic stabilities of the target derivatives 3 and 4, kinetic data and decomposition pathways were studied at 37 °C in several media.
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Journal articles
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https://hal-amu.archives-ouvertes.fr/hal-02061721
Contributor : Karine Barral Connect in order to contact the contributor
Submitted on : Friday, March 8, 2019 - 12:11:42 PM
Last modification on : Friday, May 6, 2022 - 2:56:01 PM
Contributor : Karine Barral Connect in order to contact the contributor
Submitted on : Friday, March 8, 2019 - 12:11:42 PM
Last modification on : Friday, May 6, 2022 - 2:56:01 PM
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- HAL Id : hal-02061721, version 1
- DOI : 10.1016/j.ejmech.2011.06.034
- PUBMED : 21803462
Citation
Karine Barral, Clément Weck, Nadine Payrot, Loic Roux, Céline Durafour, et al.. Acyclic nucleoside thiophosphonates as potent inhibitors of HIV and HBV replication. European Journal of Medicinal Chemistry, Elsevier, 2011, 46 (9), pp.4281-4288. ⟨10.1016/j.ejmech.2011.06.034⟩. ⟨hal-02061721⟩
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