Exploring antiviral potency of N-1 substituted pyrimidines against HIV-1 and other DNA/RNA viruses : Design, synthesis, characterization, ADMET analysis, docking, molecular dynamics and biological activity
Copyright © 2023 Elsevier Ltd. All rights reserved..
A novel series of pyrimidine derivatives, bearing modified benzimidazoles at N-1 position, has been designed, synthesized and screened as NNRTIs against HIV and as broad-spectrum antiviral agents. The molecules were screened against different HIV targets using molecular docking experiment. The docking results indicated that the molecules interacted well with the residues Lys101, Tyr181, Tyr188, Trp229, Phe227 and Tyr318 present in NNIBP of HIV-RT protein, formed quite stable complexes and, thus, behaved as probable NNRTIs. Among these compounds, 2b and 4b showed anti-HIV activity with IC50 values as 6.65 µg/mL (SI = 15.50) and 15.82 µg/mL (SI = 14.26), respectively. Similarly, compound 1a showed inhibitory property against coxsackie virus B4 and compound 3b against different viruses. Molecular dynamics simulation results unequivocally demonstrated the higher stability of the complex HIV-RT:2b than the HIV-RT:nevirapine complex. The MM/PBSA-based binding free energy (-) 114.92 kJ/mol of HIV-RT:2b complex in comparison to that of HIV-RT:nevirapine complex (-) 88.33 kJ/mol, further demonstrated the higher binding strength of 2b and thus, established the potential of compound 2b as a lead molecule as an HIV-RT inhibitor.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:106 |
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| Enthalten in: |
Computational biology and chemistry - 106(2023) vom: 09. Okt., Seite 107910 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Srivastava, Ritika [VerfasserIn] |
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| Links: |
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| Themen: |
99DK7FVK1H |
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| Anmerkungen: |
Date Completed 06.09.2023 Date Revised 06.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.compbiolchem.2023.107910 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM359239900 |
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| 100 | 1 | |a Srivastava, Ritika |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Exploring antiviral potency of N-1 substituted pyrimidines against HIV-1 and other DNA/RNA viruses |b Design, synthesis, characterization, ADMET analysis, docking, molecular dynamics and biological activity |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2023 Elsevier Ltd. All rights reserved. | ||
| 520 | |a A novel series of pyrimidine derivatives, bearing modified benzimidazoles at N-1 position, has been designed, synthesized and screened as NNRTIs against HIV and as broad-spectrum antiviral agents. The molecules were screened against different HIV targets using molecular docking experiment. The docking results indicated that the molecules interacted well with the residues Lys101, Tyr181, Tyr188, Trp229, Phe227 and Tyr318 present in NNIBP of HIV-RT protein, formed quite stable complexes and, thus, behaved as probable NNRTIs. Among these compounds, 2b and 4b showed anti-HIV activity with IC50 values as 6.65 µg/mL (SI = 15.50) and 15.82 µg/mL (SI = 14.26), respectively. Similarly, compound 1a showed inhibitory property against coxsackie virus B4 and compound 3b against different viruses. Molecular dynamics simulation results unequivocally demonstrated the higher stability of the complex HIV-RT:2b than the HIV-RT:nevirapine complex. The MM/PBSA-based binding free energy (-) 114.92 kJ/mol of HIV-RT:2b complex in comparison to that of HIV-RT:nevirapine complex (-) 88.33 kJ/mol, further demonstrated the higher binding strength of 2b and thus, established the potential of compound 2b as a lead molecule as an HIV-RT inhibitor | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a ADMET | |
| 650 | 4 | |a Docking | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a MM/PBSA | |
| 650 | 4 | |a Molecular dynamics | |
| 650 | 4 | |a Pyrimidines | |
| 650 | 7 | |a Antiviral Agents |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Reverse Transcriptase Inhibitors |2 NLM | |
| 650 | 7 | |a Nevirapine |2 NLM | |
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| 700 | 1 | |a Gupta, Sunil K |e verfasserin |4 aut | |
| 700 | 1 | |a Naaz, Farha |e verfasserin |4 aut | |
| 700 | 1 | |a Sen Gupta, Parth Sarthi |e verfasserin |4 aut | |
| 700 | 1 | |a Yadav, Madhu |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Vishal Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Panda, Saroj Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Biswal, Satyaranjan |e verfasserin |4 aut | |
| 700 | 1 | |a Rana, Malay Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Satish Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Schols, Dominique |e verfasserin |4 aut | |
| 700 | 1 | |a Singh, Ramendra K |e verfasserin |4 aut | |
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