Phosphate Derivatives of 3-Carboxyacylbetulin : SynThesis, In Vitro Anti-HIV and Molecular Docking Study
Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3-5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid-spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3',3'-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC50 (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)-spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:10 |
|---|---|
| Enthalten in: |
Biomolecules - 10(2020), 8 vom: 05. Aug. |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Marciniec, Krzysztof [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 08.09.2020 Date Revised 12.11.2023 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.3390/biom10081148 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM313395632 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM313395632 | ||
| 003 | DE-627 | ||
| 005 | 20231225150501.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/biom10081148 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1044.xml |
| 035 | |a (DE-627)NLM313395632 | ||
| 035 | |a (NLM)32764519 | ||
| 035 | |a (PII)E1148 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Marciniec, Krzysztof |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phosphate Derivatives of 3-Carboxyacylbetulin |b SynThesis, In Vitro Anti-HIV and Molecular Docking Study |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 08.09.2020 | ||
| 500 | |a Date Revised 12.11.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Lupane-type pentacyclic triterpenes such as betulin and betulinic acid play an important role in the search for new therapies that would be effective in controlling viral infections. The aim of this study was the synthesis and evaluation of in vitro anti-HIV-1 activity for phosphate derivatives of 3-carboxyacylbetulin 3-5 as well as an in silico study of new compounds as potential ligands of the C-terminal domain of the HIV-1 capsid-spacer peptide 1 (CA-CTD-SP1) as a molecular target of HIV-1 maturation inhibitors. In vitro studies showed that 28-diethoxyphosphoryl-3-O-(3',3'-dimethylsuccinyl)betulin (compound 3), the phosphate analog of bevirimat (betulinic acid derivative, HIV-1 maturation inhibitor), has IC50 (half maximal inhibitory concentration) equal to 0.02 μM. Compound 3 inhibits viral replication at a level comparable to bevirimat and is also more selective (selectivity indices = 1250 and 967, respectively). Molecular docking was used to examine the probable interaction between the phosphate derivatives of 3-carboxyacylbetulin and C-terminal domain (CTD) of the HIV-1 capsid (CA)-spacer peptide 1 (SP1) fragment of Gag protein, designated as CTD-SP1. Compared with interactions between bevirimat (BVM) and the protein, an increased number of strong interactions between ligand 3 and the protein, generated by the phosphate group, were observed. These compounds might have the potential to also inhibit SARS-CoV2 proteins, in as far as the intrinsically imprecise docking scores suggest | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a SARS-CoV-2 | |
| 650 | 4 | |a anti-HIV | |
| 650 | 4 | |a bevirimat | |
| 650 | 4 | |a triterpenes | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a Phosphates |2 NLM | |
| 650 | 7 | |a Succinates |2 NLM | |
| 650 | 7 | |a Triterpenes |2 NLM | |
| 650 | 7 | |a gag Gene Products, Human Immunodeficiency Virus |2 NLM | |
| 650 | 7 | |a betulin |2 NLM | |
| 650 | 7 | |a 6W70HN7X7O |2 NLM | |
| 650 | 7 | |a bevirimat |2 NLM | |
| 650 | 7 | |a S125DW66N8 |2 NLM | |
| 700 | 1 | |a Chrobak, Elwira |e verfasserin |4 aut | |
| 700 | 1 | |a Dąbrowska, Aleksandra |e verfasserin |4 aut | |
| 700 | 1 | |a Bębenek, Ewa |e verfasserin |4 aut | |
| 700 | 1 | |a Kadela-Tomanek, Monika |e verfasserin |4 aut | |
| 700 | 1 | |a Pęcak, Paweł |e verfasserin |4 aut | |
| 700 | 1 | |a Boryczka, Stanisław |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Biomolecules |d 2011 |g 10(2020), 8 vom: 05. Aug. |w (DE-627)NLM228347106 |x 2218-273X |7 nnns |
| 773 | 1 | 8 | |g volume:10 |g year:2020 |g number:8 |g day:05 |g month:08 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/biom10081148 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 10 |j 2020 |e 8 |b 05 |c 08 | ||