Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors
Finding new neuraminidase (N) inhibitors to improve anti-influenza treatment is necessary because of the high mutation rates of N protein. Over 3,000 flavones/flavonols and their synthesized products from the COCONUT database were performed in silico docking screening with N1-H274Y-oseltamivir prote...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
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Pensoft Publishers
2024-01-01
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| Series: | Pharmacia |
| Online Access: | https://pharmacia.pensoft.net/article/114967/download/pdf/ |
| _version_ | 1797364749531348992 |
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| author | Thi-Kim-Quy Ha Nguyen-Huan Pham-Khanh Thanh-Khiet Nguyen |
| author_facet | Thi-Kim-Quy Ha Nguyen-Huan Pham-Khanh Thanh-Khiet Nguyen |
| author_sort | Thi-Kim-Quy Ha |
| collection | DOAJ |
| description | Finding new neuraminidase (N) inhibitors to improve anti-influenza treatment is necessary because of the high mutation rates of N protein. Over 3,000 flavones/flavonols and their synthesized products from the COCONUT database were performed in silico docking screening with N1-H274Y-oseltamivir protein (PDB ID: 3CL0). Several derivatives containing nitrogen heterocyclic groups or aromatic rings showed higher anti-neuraminidase potential than that of laninamivir. Especially, the linker groups between the flavone aglycone and nitrogen heterocyclic group created the interactions with the triad of arginine residues Arg118-Arg292-Arg371, which suggested these compounds could become bifunctional inhibitors against the influenza virus strains at the sialic acid binding site and the adjacent 430-cavity position through triad of arginine residues binding. ADMET indicators and the synthesis design strategy of the most suitable compound, ethyl 4-{2-[(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy]acetyl}piperazine-1-carboxylate, were also successfully predicted and it could be a concerned candidate for further wet-lab synthesis, in vivo and clinical study. |
| first_indexed | 2024-03-08T16:39:35Z |
| format | Article |
| id | doaj.art-db54f408c1a5450e82592f76de5fdcfd |
| institution | Directory Open Access Journal |
| issn | 2603-557X |
| language | English |
| last_indexed | 2024-03-08T16:39:35Z |
| publishDate | 2024-01-01 |
| publisher | Pensoft Publishers |
| record_format | Article |
| series | Pharmacia |
| spelling | doaj.art-db54f408c1a5450e82592f76de5fdcfd2024-01-05T11:00:08ZengPensoft PublishersPharmacia2603-557X2024-01-017111010.3897/pharmacia.71.e114967114967Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitorsThi-Kim-Quy Ha0Nguyen-Huan Pham-Khanh1Thanh-Khiet Nguyen2Can Tho UniversityCan Tho UniversityCan Tho UniversityFinding new neuraminidase (N) inhibitors to improve anti-influenza treatment is necessary because of the high mutation rates of N protein. Over 3,000 flavones/flavonols and their synthesized products from the COCONUT database were performed in silico docking screening with N1-H274Y-oseltamivir protein (PDB ID: 3CL0). Several derivatives containing nitrogen heterocyclic groups or aromatic rings showed higher anti-neuraminidase potential than that of laninamivir. Especially, the linker groups between the flavone aglycone and nitrogen heterocyclic group created the interactions with the triad of arginine residues Arg118-Arg292-Arg371, which suggested these compounds could become bifunctional inhibitors against the influenza virus strains at the sialic acid binding site and the adjacent 430-cavity position through triad of arginine residues binding. ADMET indicators and the synthesis design strategy of the most suitable compound, ethyl 4-{2-[(5-hydroxy-4-oxo-2-phenyl-4H-chromen-7-yl)oxy]acetyl}piperazine-1-carboxylate, were also successfully predicted and it could be a concerned candidate for further wet-lab synthesis, in vivo and clinical study.https://pharmacia.pensoft.net/article/114967/download/pdf/ |
| spellingShingle | Thi-Kim-Quy Ha Nguyen-Huan Pham-Khanh Thanh-Khiet Nguyen Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors Pharmacia |
| title | Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors |
| title_full | Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors |
| title_fullStr | Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors |
| title_full_unstemmed | Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors |
| title_short | Molecular docking screening, dynamics simulations, ADMET, and semi-synthesis prediction of flavones and flavonols from the COCONUT database as potent bifunctional neuraminidase inhibitors |
| title_sort | molecular docking screening dynamics simulations admet and semi synthesis prediction of flavones and flavonols from the coconut database as potent bifunctional neuraminidase inhibitors |
| url | https://pharmacia.pensoft.net/article/114967/download/pdf/ |
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