The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation
Here, we report the synthesis, enzyme inhibition and structure–activity relationship studies of a new potent class of HIV-1 protease inhibitors, which contain a pseudo-symmetric hydroxyethylamine core and heteroarylcarboxyamide moieties. The simple synthetic pathway furnished nine compounds in a few...
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2021
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oai:doaj.org-article:9cb7dd769a6d4caca673db4e89ccd6f32021-11-25T16:52:21ZThe Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation10.3390/biom111115842218-273Xhttps://doaj.org/article/9cb7dd769a6d4caca673db4e89ccd6f32021-10-01T00:00:00Zhttps://www.mdpi.com/2218-273X/11/11/1584https://doaj.org/toc/2218-273XHere, we report the synthesis, enzyme inhibition and structure–activity relationship studies of a new potent class of HIV-1 protease inhibitors, which contain a pseudo-symmetric hydroxyethylamine core and heteroarylcarboxyamide moieties. The simple synthetic pathway furnished nine compounds in a few steps with high yields. The compounds were designed taking into account our previous results on other series of inhibitors with different substituents at P’ and P’’ and different ways of linking them to the inhibitor core. Potent inhibitory activity was obtained with nanomolar IC<sub>50</sub> values measured with a standard fluorimetric test in 100 mM MES buffer, pH 5.5, containing 400 mM NaCl, 1 mM EDTA, 1 mM DTT and 1 mg/ml BSA. Compounds <b>9a</b>–<b>c</b>, containing the indole ring in P1, exhibited an HIV-1 protease inhibitory activity more powerful than darunavir in the same assay. To obtain molecular insight into the binding properties of these compounds, docking analysis was performed, and their binding properties were also compared.Rosarita D’OrsiMaria FunicelloTeresa LauritaPaolo LupattelliFederico BertiLucia ChiummientoMDPI AGarticleHIV-protease inhibitorspseudo-symmetric coreheteroaryl carboxyamidessynthesisbiological screeningmodelingMicrobiologyQR1-502ENBiomolecules, Vol 11, Iss 1584, p 1584 (2021) |
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DOAJ |
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DOAJ |
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EN |
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HIV-protease inhibitors pseudo-symmetric core heteroaryl carboxyamides synthesis biological screening modeling Microbiology QR1-502 |
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HIV-protease inhibitors pseudo-symmetric core heteroaryl carboxyamides synthesis biological screening modeling Microbiology QR1-502 Rosarita D’Orsi Maria Funicello Teresa Laurita Paolo Lupattelli Federico Berti Lucia Chiummiento The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation |
| description |
Here, we report the synthesis, enzyme inhibition and structure–activity relationship studies of a new potent class of HIV-1 protease inhibitors, which contain a pseudo-symmetric hydroxyethylamine core and heteroarylcarboxyamide moieties. The simple synthetic pathway furnished nine compounds in a few steps with high yields. The compounds were designed taking into account our previous results on other series of inhibitors with different substituents at P’ and P’’ and different ways of linking them to the inhibitor core. Potent inhibitory activity was obtained with nanomolar IC<sub>50</sub> values measured with a standard fluorimetric test in 100 mM MES buffer, pH 5.5, containing 400 mM NaCl, 1 mM EDTA, 1 mM DTT and 1 mg/ml BSA. Compounds <b>9a</b>–<b>c</b>, containing the indole ring in P1, exhibited an HIV-1 protease inhibitory activity more powerful than darunavir in the same assay. To obtain molecular insight into the binding properties of these compounds, docking analysis was performed, and their binding properties were also compared. |
| format |
article |
| author |
Rosarita D’Orsi Maria Funicello Teresa Laurita Paolo Lupattelli Federico Berti Lucia Chiummiento |
| author_facet |
Rosarita D’Orsi Maria Funicello Teresa Laurita Paolo Lupattelli Federico Berti Lucia Chiummiento |
| author_sort |
Rosarita D’Orsi |
| title |
The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation |
| title_short |
The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation |
| title_full |
The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation |
| title_fullStr |
The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation |
| title_full_unstemmed |
The Pseudo-Symmetric <i>N</i>-benzyl Hydroxyethylamine Core in a New Series of Heteroarylcarboxyamide HIV-1 Pr Inhibitors: Synthesis, Molecular Modeling and Biological Evaluation |
| title_sort |
pseudo-symmetric <i>n</i>-benzyl hydroxyethylamine core in a new series of heteroarylcarboxyamide hiv-1 pr inhibitors: synthesis, molecular modeling and biological evaluation |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/9cb7dd769a6d4caca673db4e89ccd6f3 |
| work_keys_str_mv |
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| _version_ |
1718412912366714880 |