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In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)

Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii. In this study, we have screened natu...

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Autores principales: Vasudevan, Aparna, Kesavan, Dinesh Kumar, Wu, Liang, Su, Zhaoliang, Wang, Shengjun, Ramasamy, Mohan Kumar, Hopper, Waheeta, Xu, Huaxi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966755/
https://www.ncbi.nlm.nih.gov/pubmed/35372567
http://dx.doi.org/10.1155/2022/4230788
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author Vasudevan, Aparna
Kesavan, Dinesh Kumar
Wu, Liang
Su, Zhaoliang
Wang, Shengjun
Ramasamy, Mohan Kumar
Hopper, Waheeta
Xu, Huaxi
author_facet Vasudevan, Aparna
Kesavan, Dinesh Kumar
Wu, Liang
Su, Zhaoliang
Wang, Shengjun
Ramasamy, Mohan Kumar
Hopper, Waheeta
Xu, Huaxi
author_sort Vasudevan, Aparna
collection PubMed
description Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii. In this study, we have screened natural compounds as a possible inhibitor against the NDM-1 β-lactamase enzyme from A. baumannii using a combination of in silico methods and in vitro evaluation. The database of natural compounds was screened against NDM-1 protein, using Glide docking, followed by QM-polarised ligand docking (QPLD). When the screened hits were validated in vitro, withaferin A and mangiferin had good IC(50) values in reducing the activity of NDM-1 enzymes, and their fractional inhibitory concentration index (FICI) was ascertained in combination with imipenem. The withaferin A and mangiferin-NDM-1 docking complexes were analyzed for structural stability by molecular dynamic simulation analysis using GROMACS for 100 ns. The molecular properties of the natural compounds were then calculated using density functional theory (DFT). Withaferin A and mangiferin showed promising inhibitory activity and can be a natural compound candidate inhibitor synergistically used along with carbapenems against NDM-1 producing A. baumannii.
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spelling pubmed-89667552022-03-31 In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1) Vasudevan, Aparna Kesavan, Dinesh Kumar Wu, Liang Su, Zhaoliang Wang, Shengjun Ramasamy, Mohan Kumar Hopper, Waheeta Xu, Huaxi Biomed Res Int Research Article Antibiotic resistance is one of the significant problems globally; there is an increase in resistance with introducing every new class of antibiotics. Further, this has become one of the reasons for arising of new resistance mechanisms in Acinetobacter baumannii. In this study, we have screened natural compounds as a possible inhibitor against the NDM-1 β-lactamase enzyme from A. baumannii using a combination of in silico methods and in vitro evaluation. The database of natural compounds was screened against NDM-1 protein, using Glide docking, followed by QM-polarised ligand docking (QPLD). When the screened hits were validated in vitro, withaferin A and mangiferin had good IC(50) values in reducing the activity of NDM-1 enzymes, and their fractional inhibitory concentration index (FICI) was ascertained in combination with imipenem. The withaferin A and mangiferin-NDM-1 docking complexes were analyzed for structural stability by molecular dynamic simulation analysis using GROMACS for 100 ns. The molecular properties of the natural compounds were then calculated using density functional theory (DFT). Withaferin A and mangiferin showed promising inhibitory activity and can be a natural compound candidate inhibitor synergistically used along with carbapenems against NDM-1 producing A. baumannii. Hindawi 2022-03-10 /pmc/articles/PMC8966755/ /pubmed/35372567 http://dx.doi.org/10.1155/2022/4230788 Text en Copyright © 2022 Aparna Vasudevan et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Vasudevan, Aparna
Kesavan, Dinesh Kumar
Wu, Liang
Su, Zhaoliang
Wang, Shengjun
Ramasamy, Mohan Kumar
Hopper, Waheeta
Xu, Huaxi
In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)
title In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)
title_full In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)
title_fullStr In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)
title_full_unstemmed In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)
title_short In Silico and In Vitro Screening of Natural Compounds as Broad-Spectrum β-Lactamase Inhibitors against Acinetobacter baumannii New Delhi Metallo-β-lactamase-1 (NDM-1)
title_sort in silico and in vitro screening of natural compounds as broad-spectrum β-lactamase inhibitors against acinetobacter baumannii new delhi metallo-β-lactamase-1 (ndm-1)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8966755/
https://www.ncbi.nlm.nih.gov/pubmed/35372567
http://dx.doi.org/10.1155/2022/4230788
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