Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

Raimon Puig-De-La-Bellacasa; Laura Giménez; Sofia Pettersson; Rosalia Pascual; Encarna Gonzalo; José A. Esté; Bonaventura Clotet; José I. Borrell; Jordi Teixidó

doi:10.1016/j.ejmech.2012.04.038

Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

Raimon Puig-De-La-Bellacasa, Laura Giménez, Sofia Pettersson, Rosalia Pascual, Encarna Gonzalo, José A. Esté, Bonaventura Clotet, José I. Borrell, Jordi Teixidó

Department of Medicine

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

18 Citations (Scopus)

Abstract

New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25). © 2012 Elsevier Masson SAS. All rights reserved.

Original language	English
Pages (from-to)	159-174
Journal	European Journal of Medicinal Chemistry
Volume	54
DOIs	https://doi.org/10.1016/j.ejmech.2012.04.038
Publication status	Published - 1 Aug 2012

Keywords

Antiviral activity
Combinatorial design
Diversity selection HIV-1
NNRTIs HEPT

UN SDGs

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

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10.1016/j.ejmech.2012.04.038

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Puig-De-La-Bellacasa, R., Giménez, L., Pettersson, S., Pascual, R., Gonzalo, E., Esté, J. A., Clotet, B., Borrell, J. I., & Teixidó, J. (2012). Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors. European Journal of Medicinal Chemistry, 54, 159-174. https://doi.org/10.1016/j.ejmech.2012.04.038

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title = "Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors",

abstract = "New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25). {\textcopyright} 2012 Elsevier Masson SAS. All rights reserved.",

keywords = "Antiviral activity, Combinatorial design, Diversity selection HIV-1, NNRTIs HEPT",

author = "Raimon Puig-De-La-Bellacasa and Laura Gim{\'e}nez and Sofia Pettersson and Rosalia Pascual and Encarna Gonzalo and Est{\'e}, {Jos{\'e} A.} and Bonaventura Clotet and Borrell, {Jos{\'e} I.} and Jordi Teixid{\'o}",

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Puig-De-La-Bellacasa, R, Giménez, L, Pettersson, S, Pascual, R, Gonzalo, E, Esté, JA, Clotet, B, Borrell, JI & Teixidó, J 2012, 'Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors', European Journal of Medicinal Chemistry, vol. 54, pp. 159-174. https://doi.org/10.1016/j.ejmech.2012.04.038

Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors. / Puig-De-La-Bellacasa, Raimon; Giménez, Laura; Pettersson, Sofia et al.

In: European Journal of Medicinal Chemistry, Vol. 54, 01.08.2012, p. 159-174.

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

TY - JOUR

T1 - Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

AU - Puig-De-La-Bellacasa, Raimon

AU - Giménez, Laura

AU - Pettersson, Sofia

AU - Pascual, Rosalia

AU - Gonzalo, Encarna

AU - Esté, José A.

AU - Clotet, Bonaventura

AU - Borrell, José I.

AU - Teixidó, Jordi

PY - 2012/8/1

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N2 - New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25). © 2012 Elsevier Masson SAS. All rights reserved.

AB - New analogues of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were synthesized and evaluated for their in vitro activities against HIV-1 in MT-4 cell cultures. Chemical diversity was introduced in 4 of the six positions of the core and the influence of each substituent was studied. This library was built on the basis of a rational diversity analysis with the objective of maximizing diversity and thus, the activity range with a minimum number of synthesized compounds. Among them, 2{1,2,3,1} and 2{1,2,3,4} exhibited the most potent anti-HIV-1 activities (EC50 = 0.015 μg/mL; 0.046 μM, SI >1667) and (EC50 = 0.025 μg/mL; 0.086 μM, SI >1000), respectively, which were about 71-fold and 38-fold more active than the reference compound HEPT (EC50 = 1.01 μg/mL; 3.27 μM, SI >25). © 2012 Elsevier Masson SAS. All rights reserved.

KW - Antiviral activity

KW - Combinatorial design

KW - Diversity selection HIV-1

KW - NNRTIs HEPT

U2 - 10.1016/j.ejmech.2012.04.038

DO - 10.1016/j.ejmech.2012.04.038

M3 - Article

VL - 54

SP - 159

EP - 174

ER -

Diverse combinatorial design, synthesis and in vitro evaluation of new HEPT analogues as potential non-nucleoside HIV-1 reverse transcription inhibitors

Abstract

Keywords

UN SDGs

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