Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies
This study aims to determine the antibacterial efficacy of a bioactive phytochemical quercetin (QUR), compared to the reference antibiotic ciprofloxacin (CIP), using in vitro and in silico approaches. Following molecular docking, QUR showed strong affinity to the druggable targets from bacteria: Sor...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-06-01
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| Series: | Chemical Physics Impact |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667022424000458 |
| _version_ | 1797322435100409856 |
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| author | Golak Majumdar Shyamapada Mandal |
| author_facet | Golak Majumdar Shyamapada Mandal |
| author_sort | Golak Majumdar |
| collection | DOAJ |
| description | This study aims to determine the antibacterial efficacy of a bioactive phytochemical quercetin (QUR), compared to the reference antibiotic ciprofloxacin (CIP), using in vitro and in silico approaches. Following molecular docking, QUR showed strong affinity to the druggable targets from bacteria: Sortase B, Toxic Shock Syndrome Toxin-1, Multidrug Efflux Pump AdeJ and LasR, with binding energies –6.9 to –10.3 kcal/mol. CIP displayed binding energies –7.3 to –7.4 kcal/mol against the target proteins. QUR had stronger efficacy against MEPJ (binding energy: -8.1 kcal/mol) and LasR (binding energy: -10.3 kcal/mol), compared to CIP having binding energies -7.4 and -7.3 kcal/mol, respectively. Molecular dynamics simulation validated the formation of LasR complex with QUR, which was energetically more stable compared to the LasR-CIP complex. Disc diffusion method, using nutrient agar medium, demonstrated antibacterial activity of QUR against both gram-negative (Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus, Streptococcus pneumonia) bacteria with zone diameter of inhibition 10–23 mm and 7–21 mm, respectively. QUR displayed synergistic effect, with growth inhibitory index (GII) values of 0.65–1.15, combined with PIP. QUR-CEF combination displayed synergy against E. coli, P. aeruginosa, and S. pneumoniae with GIIs 0.60–0.73. Pharmacokinetics studies for QUR revealed acceptable parametric values, comparable to that of CIP. Thus, the current integrated in silico and in vitro analysis authenticated QUR as a strong lead molecule to combat bacterial infections, using QUR alone or in combination with conventionally used antibiotics (PIP and CEF). For further validation of our results, clinical experiments are suggested. |
| first_indexed | 2024-03-08T05:14:19Z |
| format | Article |
| id | doaj.art-928961c441c2447e8483bfd31805ae5a |
| institution | Directory Open Access Journal |
| issn | 2667-0224 |
| language | English |
| last_indexed | 2024-03-08T05:14:19Z |
| publishDate | 2024-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Chemical Physics Impact |
| spelling | doaj.art-928961c441c2447e8483bfd31805ae5a2024-02-07T04:46:03ZengElsevierChemical Physics Impact2667-02242024-06-018100501Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studiesGolak Majumdar0Shyamapada Mandal1Department of Zoology, University of Gour Banga, Malda-732103, IndiaCorresponding author.; Department of Zoology, University of Gour Banga, Malda-732103, IndiaThis study aims to determine the antibacterial efficacy of a bioactive phytochemical quercetin (QUR), compared to the reference antibiotic ciprofloxacin (CIP), using in vitro and in silico approaches. Following molecular docking, QUR showed strong affinity to the druggable targets from bacteria: Sortase B, Toxic Shock Syndrome Toxin-1, Multidrug Efflux Pump AdeJ and LasR, with binding energies –6.9 to –10.3 kcal/mol. CIP displayed binding energies –7.3 to –7.4 kcal/mol against the target proteins. QUR had stronger efficacy against MEPJ (binding energy: -8.1 kcal/mol) and LasR (binding energy: -10.3 kcal/mol), compared to CIP having binding energies -7.4 and -7.3 kcal/mol, respectively. Molecular dynamics simulation validated the formation of LasR complex with QUR, which was energetically more stable compared to the LasR-CIP complex. Disc diffusion method, using nutrient agar medium, demonstrated antibacterial activity of QUR against both gram-negative (Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus, Streptococcus pneumonia) bacteria with zone diameter of inhibition 10–23 mm and 7–21 mm, respectively. QUR displayed synergistic effect, with growth inhibitory index (GII) values of 0.65–1.15, combined with PIP. QUR-CEF combination displayed synergy against E. coli, P. aeruginosa, and S. pneumoniae with GIIs 0.60–0.73. Pharmacokinetics studies for QUR revealed acceptable parametric values, comparable to that of CIP. Thus, the current integrated in silico and in vitro analysis authenticated QUR as a strong lead molecule to combat bacterial infections, using QUR alone or in combination with conventionally used antibiotics (PIP and CEF). For further validation of our results, clinical experiments are suggested.http://www.sciencedirect.com/science/article/pii/S2667022424000458QuercetinMolecular dockingMolecular dynamic simulationsAntibacterial activityADMET profiles |
| spellingShingle | Golak Majumdar Shyamapada Mandal Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies Chemical Physics Impact Quercetin Molecular docking Molecular dynamic simulations Antibacterial activity ADMET profiles |
| title | Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies |
| title_full | Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies |
| title_fullStr | Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies |
| title_full_unstemmed | Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies |
| title_short | Evaluation of broad-spectrum antibacterial efficacy of quercetin by molecular docking, molecular dynamics simulation and in vitro studies |
| title_sort | evaluation of broad spectrum antibacterial efficacy of quercetin by molecular docking molecular dynamics simulation and in vitro studies |
| topic | Quercetin Molecular docking Molecular dynamic simulations Antibacterial activity ADMET profiles |
| url | http://www.sciencedirect.com/science/article/pii/S2667022424000458 |
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