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Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1
Nucleoside reverse transcriptase inhibitors are the first class of drugs to be approved by the FDA for the suppression of HIV-1 and are widely used for this purpose in combination with drugs of other classes. Despite the progress in HIV-1 treatment, there is still the need to develop novel efficient...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610023/ https://www.ncbi.nlm.nih.gov/pubmed/37896149 http://dx.doi.org/10.3390/pharmaceutics15102389 |
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author | Glumakova, Ksenia Ivanov, Georgy Vedernikova, Valeria Shyrokova, Lena Lebedev, Timofey Stomakhin, Andrei Zenchenko, Anastasia Oslovsky, Vladimir Drenichev, Mikhail Prassolov, Vladimir Spirin, Pavel |
author_facet | Glumakova, Ksenia Ivanov, Georgy Vedernikova, Valeria Shyrokova, Lena Lebedev, Timofey Stomakhin, Andrei Zenchenko, Anastasia Oslovsky, Vladimir Drenichev, Mikhail Prassolov, Vladimir Spirin, Pavel |
author_sort | Glumakova, Ksenia |
collection | PubMed |
description | Nucleoside reverse transcriptase inhibitors are the first class of drugs to be approved by the FDA for the suppression of HIV-1 and are widely used for this purpose in combination with drugs of other classes. Despite the progress in HIV-1 treatment, there is still the need to develop novel efficient antivirals. Here the efficiency of HIV-1 inhibition by a set of original 5-substituted uridine nucleosides was studied. We used the replication deficient human immunodeficiency virus (HIV-1)-based lentiviral particles and identified that among the studied compounds, 2′,3′-isopropylidene-5-iodouridine was shown to cause anti-HIV-1 activity. Importantly, no toxic action of this compound against the cells of T-cell origin was found. We determined that this compound is significantly more efficient at suppressing HIV-1 compared to Azidothymidine (AZT) when taken at the high non-toxic concentrations. We did not find any profit when using AZT in combination with 2′,3′-isopropylidene-5-iodouridine. 2′,3′-Isopropylidene-5-iodouridine acts synergistically to repress HIV-1 when combined with the CDK4/6 inhibitor Palbociclib in low non-toxic concentration. No synergistic antiviral action was detected when AZT was combined with Palbociclib. We suggest 2′,3′-isopropylidene-5-iodouridine as a novel perspective non-toxic compound that may be used for HIV-l suppression. |
format | Online Article Text |
id | pubmed-10610023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-106100232023-10-28 Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 Glumakova, Ksenia Ivanov, Georgy Vedernikova, Valeria Shyrokova, Lena Lebedev, Timofey Stomakhin, Andrei Zenchenko, Anastasia Oslovsky, Vladimir Drenichev, Mikhail Prassolov, Vladimir Spirin, Pavel Pharmaceutics Article Nucleoside reverse transcriptase inhibitors are the first class of drugs to be approved by the FDA for the suppression of HIV-1 and are widely used for this purpose in combination with drugs of other classes. Despite the progress in HIV-1 treatment, there is still the need to develop novel efficient antivirals. Here the efficiency of HIV-1 inhibition by a set of original 5-substituted uridine nucleosides was studied. We used the replication deficient human immunodeficiency virus (HIV-1)-based lentiviral particles and identified that among the studied compounds, 2′,3′-isopropylidene-5-iodouridine was shown to cause anti-HIV-1 activity. Importantly, no toxic action of this compound against the cells of T-cell origin was found. We determined that this compound is significantly more efficient at suppressing HIV-1 compared to Azidothymidine (AZT) when taken at the high non-toxic concentrations. We did not find any profit when using AZT in combination with 2′,3′-isopropylidene-5-iodouridine. 2′,3′-Isopropylidene-5-iodouridine acts synergistically to repress HIV-1 when combined with the CDK4/6 inhibitor Palbociclib in low non-toxic concentration. No synergistic antiviral action was detected when AZT was combined with Palbociclib. We suggest 2′,3′-isopropylidene-5-iodouridine as a novel perspective non-toxic compound that may be used for HIV-l suppression. MDPI 2023-09-27 /pmc/articles/PMC10610023/ /pubmed/37896149 http://dx.doi.org/10.3390/pharmaceutics15102389 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Glumakova, Ksenia Ivanov, Georgy Vedernikova, Valeria Shyrokova, Lena Lebedev, Timofey Stomakhin, Andrei Zenchenko, Anastasia Oslovsky, Vladimir Drenichev, Mikhail Prassolov, Vladimir Spirin, Pavel Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 |
title | Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 |
title_full | Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 |
title_fullStr | Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 |
title_full_unstemmed | Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 |
title_short | Nucleoside Analog 2′,3′-Isopropylidene-5-Iodouridine as Novel Efficient Inhibitor of HIV-1 |
title_sort | nucleoside analog 2′,3′-isopropylidene-5-iodouridine as novel efficient inhibitor of hiv-1 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610023/ https://www.ncbi.nlm.nih.gov/pubmed/37896149 http://dx.doi.org/10.3390/pharmaceutics15102389 |
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