Abd Kakhar Umar, Dhritiman Roy, Mohnad Abdalla, Yosra Modafer, Nawal Al-Hoshani, Han Yu, James H Zothantluanga
{"title":"通过对金合欢(Acacia pennata)和金合欢属(Bridelia retusa)植物进行室内筛选,发现 pinocembrin-7-O-β-D-glucopyranoside 是一种很有前景的β-内酰胺酶抑制剂,可用于对抗抗生素耐药性。","authors":"Abd Kakhar Umar, Dhritiman Roy, Mohnad Abdalla, Yosra Modafer, Nawal Al-Hoshani, Han Yu, James H Zothantluanga","doi":"10.1080/07391102.2023.2248272","DOIUrl":null,"url":null,"abstract":"<p><p>The β-lactamase of <i>Pseudomonas aeruginosa</i> is known to degrade β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems. With the discovery of an extended-spectrum β-lactamase in a clinical isolate of <i>P. aeruginosa</i>, the bacterium has become multi-drug resistant. In this study, we aim to identify new β-lactamase inhibitors by virtually screening a total of 43 phytocompounds from two Indian medicinal plants. In the molecular docking studies, pinocembrin-7-<i>O</i>-β-D-glucopyranoside (P7G) (-9.6 kcal/mol) from <i>Acacia pennata</i> and ellagic acid (EA) (-9.2 kcal/mol) from <i>Bridelia retusa</i> had lower binding energy than moxalactam (-8.4 kcal/mol). P7G and EA formed 5 (<i>Ser62, Asn125, Asn163, Thr209,</i> and <i>Ser230</i>) and 4 (<i>Lys65, Ser123, Asn125,</i> and <i>Glu159</i>) conventional hydrogens bonds with the active site residues. 100 ns MD simulations revealed that moxalactam and P7G (but not EA) were able to form a stable complex. The binding free energy calculations further revealed that P7G (-59.6526 kcal/mol) formed the most stable complex with β-lactamase when compared to moxalactam (-46.5669 kcal/mol) and EA (-28.4505 kcal/mol). The HOMO-LUMO and other DFT parameters support the stability and chemical reactivity of P7G at the active site of β-lactamase. P7G passed all the toxicity tests and bioavailability tests indicating that it possesses drug-likeness. Among the studied compounds, we identified P7G of <i>A. pennata</i> as the most promising phytocompound to combat antibiotic resistance by potentially inhibiting the β-lactamase of <i>P. aeruginosa</i>.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"<i>In-silico</i> screening of <i>Acacia pennata</i> and <i>Bridelia retusa</i> reveals pinocembrin-7-O-β-D-glucopyranoside as a promising β-lactamase inhibitor to combat antibiotic resistance.\",\"authors\":\"Abd Kakhar Umar, Dhritiman Roy, Mohnad Abdalla, Yosra Modafer, Nawal Al-Hoshani, Han Yu, James H Zothantluanga\",\"doi\":\"10.1080/07391102.2023.2248272\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The β-lactamase of <i>Pseudomonas aeruginosa</i> is known to degrade β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems. With the discovery of an extended-spectrum β-lactamase in a clinical isolate of <i>P. aeruginosa</i>, the bacterium has become multi-drug resistant. In this study, we aim to identify new β-lactamase inhibitors by virtually screening a total of 43 phytocompounds from two Indian medicinal plants. In the molecular docking studies, pinocembrin-7-<i>O</i>-β-D-glucopyranoside (P7G) (-9.6 kcal/mol) from <i>Acacia pennata</i> and ellagic acid (EA) (-9.2 kcal/mol) from <i>Bridelia retusa</i> had lower binding energy than moxalactam (-8.4 kcal/mol). P7G and EA formed 5 (<i>Ser62, Asn125, Asn163, Thr209,</i> and <i>Ser230</i>) and 4 (<i>Lys65, Ser123, Asn125,</i> and <i>Glu159</i>) conventional hydrogens bonds with the active site residues. 100 ns MD simulations revealed that moxalactam and P7G (but not EA) were able to form a stable complex. The binding free energy calculations further revealed that P7G (-59.6526 kcal/mol) formed the most stable complex with β-lactamase when compared to moxalactam (-46.5669 kcal/mol) and EA (-28.4505 kcal/mol). The HOMO-LUMO and other DFT parameters support the stability and chemical reactivity of P7G at the active site of β-lactamase. P7G passed all the toxicity tests and bioavailability tests indicating that it possesses drug-likeness. Among the studied compounds, we identified P7G of <i>A. pennata</i> as the most promising phytocompound to combat antibiotic resistance by potentially inhibiting the β-lactamase of <i>P. aeruginosa</i>.Communicated by Ramaswamy H. 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In-silico screening of Acacia pennata and Bridelia retusa reveals pinocembrin-7-O-β-D-glucopyranoside as a promising β-lactamase inhibitor to combat antibiotic resistance.
The β-lactamase of Pseudomonas aeruginosa is known to degrade β-lactam antibiotics such as penicillins, cephalosporins, monobactams, and carbapenems. With the discovery of an extended-spectrum β-lactamase in a clinical isolate of P. aeruginosa, the bacterium has become multi-drug resistant. In this study, we aim to identify new β-lactamase inhibitors by virtually screening a total of 43 phytocompounds from two Indian medicinal plants. In the molecular docking studies, pinocembrin-7-O-β-D-glucopyranoside (P7G) (-9.6 kcal/mol) from Acacia pennata and ellagic acid (EA) (-9.2 kcal/mol) from Bridelia retusa had lower binding energy than moxalactam (-8.4 kcal/mol). P7G and EA formed 5 (Ser62, Asn125, Asn163, Thr209, and Ser230) and 4 (Lys65, Ser123, Asn125, and Glu159) conventional hydrogens bonds with the active site residues. 100 ns MD simulations revealed that moxalactam and P7G (but not EA) were able to form a stable complex. The binding free energy calculations further revealed that P7G (-59.6526 kcal/mol) formed the most stable complex with β-lactamase when compared to moxalactam (-46.5669 kcal/mol) and EA (-28.4505 kcal/mol). The HOMO-LUMO and other DFT parameters support the stability and chemical reactivity of P7G at the active site of β-lactamase. P7G passed all the toxicity tests and bioavailability tests indicating that it possesses drug-likeness. Among the studied compounds, we identified P7G of A. pennata as the most promising phytocompound to combat antibiotic resistance by potentially inhibiting the β-lactamase of P. aeruginosa.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.