Petra/Osiris/Molinspiration and Molecular Docking Analyses of 3-Hydroxy-Indolin-2-one Derivatives as Potential Antiviral Agents
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Studies on the interaction between bioactive molecules and HIV-1 virus have been the focus of recent research in the scope of medicinal chemistry and pharmacology.
OBJECTIVE: Investigating the structural parameters and physico-chemical properties of elucidating and identifying the antiviral pharmacophore sites.
METHODS: A mixed computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of 22 3-hydroxy-indolin-2-one derivatives of diacetyl-L-tartaric acid and aromatic amines containing combined antiviral/antitumor/antibacterial pharmacophore sites. Molecular docking study was carried out with HIV-1 integrase (pdb ID: 5KGX) in order to provide information about interactions in the binding site of the enzyme.
RESULTS: The POM analyses of physico-chemical properties and geometrical parameters of compounds 3a-5j, show that they are bearing a two combined (O,O)-pockets leading to a special platform which is able to coordinate two transition metals. The increased activity of series 3a-5j, as compared to standard drugs, contains (Osp2,O sp3,O sp2)-pharmacophore site. The increase in bioactivity from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence of π-charge transfer from para-bromo-phenyl to its amid group (COδ---NHδ+). Similar to the indole-based reference ligand (pdb: 7SK), compound 3d forms hydrogen bonding interactions between the residues Glu170, Thr174 and His171 of HIV-1 integrase in the catalytic core domain of the enzyme.
CONCLUSION: Study confirmed the importance of oxygen atoms, especially from the methoxy group of the phenyl ring, and electrophilic amide nitrogen atom for the formation of interactions.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2021 |
|---|---|
| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
Current computer-aided drug design - 17(2021), 1 vom: 02., Seite 123-133 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Hadda, Taibi Ben [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 21.10.2021 Date Revised 21.10.2021 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.2174/1573409916666191226110029 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM304789356 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM304789356 | ||
| 003 | DE-627 | ||
| 005 | 20231225115733.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.2174/1573409916666191226110029 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1015.xml |
| 035 | |a (DE-627)NLM304789356 | ||
| 035 | |a (NLM)31878861 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Hadda, Taibi Ben |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Petra/Osiris/Molinspiration and Molecular Docking Analyses of 3-Hydroxy-Indolin-2-one Derivatives as Potential Antiviral Agents |
| 264 | 1 | |c 2021 | |
| 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 21.10.2021 | ||
| 500 | |a Date Revised 21.10.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Studies on the interaction between bioactive molecules and HIV-1 virus have been the focus of recent research in the scope of medicinal chemistry and pharmacology | ||
| 520 | |a OBJECTIVE: Investigating the structural parameters and physico-chemical properties of elucidating and identifying the antiviral pharmacophore sites | ||
| 520 | |a METHODS: A mixed computational Petra/Osiris/Molinspiration/DFT (POM/DFT) based model has been developed for the identification of physico-chemical parameters governing the bioactivity of 22 3-hydroxy-indolin-2-one derivatives of diacetyl-L-tartaric acid and aromatic amines containing combined antiviral/antitumor/antibacterial pharmacophore sites. Molecular docking study was carried out with HIV-1 integrase (pdb ID: 5KGX) in order to provide information about interactions in the binding site of the enzyme | ||
| 520 | |a RESULTS: The POM analyses of physico-chemical properties and geometrical parameters of compounds 3a-5j, show that they are bearing a two combined (O,O)-pockets leading to a special platform which is able to coordinate two transition metals. The increased activity of series 3a-5j, as compared to standard drugs, contains (Osp2,O sp3,O sp2)-pharmacophore site. The increase in bioactivity from 4b (R1, R2 = H, H) to 3d (R1, R2 = 4-Br, 2-OCH3) could be attributed to the existence of π-charge transfer from para-bromo-phenyl to its amid group (COδ---NHδ+). Similar to the indole-based reference ligand (pdb: 7SK), compound 3d forms hydrogen bonding interactions between the residues Glu170, Thr174 and His171 of HIV-1 integrase in the catalytic core domain of the enzyme | ||
| 520 | |a CONCLUSION: Study confirmed the importance of oxygen atoms, especially from the methoxy group of the phenyl ring, and electrophilic amide nitrogen atom for the formation of interactions | ||
| 650 | 4 | |a Comparative Study | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 3-Hydroxy-indolin-2-ones | |
| 650 | 4 | |a HIV antiviral activity | |
| 650 | 4 | |a HIV-1 integrase | |
| 650 | 4 | |a POM analyses | |
| 650 | 4 | |a molecular docking | |
| 650 | 4 | |a pharmacophore | |
| 650 | 7 | |a 3-hydroxyindolin-2-one |2 NLM | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a HIV Integrase Inhibitors |2 NLM | |
| 650 | 7 | |a Indoles |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a HIV Integrase |2 NLM | |
| 650 | 7 | |a EC 2.7.7.- |2 NLM | |
| 650 | 7 | |a p31 integrase protein, Human immunodeficiency virus 1 |2 NLM | |
| 650 | 7 | |a YY6481J2FF |2 NLM | |
| 700 | 1 | |a Rastija, Vesna |e verfasserin |4 aut | |
| 700 | 1 | |a AlMalki, Faisal |e verfasserin |4 aut | |
| 700 | 1 | |a Titi, Abderrahim |e verfasserin |4 aut | |
| 700 | 1 | |a Touzani, Rachid |e verfasserin |4 aut | |
| 700 | 1 | |a Mabkhot, Yahia N |e verfasserin |4 aut | |
| 700 | 1 | |a Khalid, Shah |e verfasserin |4 aut | |
| 700 | 1 | |a Zarrouk, Abdelkader |e verfasserin |4 aut | |
| 700 | 1 | |a Siddiqui, Bina S |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Current computer-aided drug design |d 2008 |g 17(2021), 1 vom: 02., Seite 123-133 |w (DE-627)NLM191691046 |x 1875-6697 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2021 |g number:1 |g day:02 |g pages:123-133 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.2174/1573409916666191226110029 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 17 |j 2021 |e 1 |b 02 |h 123-133 | ||