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Screening of potential lead molecules against prioritised targets of multi-drug-resistant-Acinetobacter baumannii - insights from molecular docking, molecular dynamic simulations and in vitro assays.
J Biomol Struct Dyn. 2019 Mar; 37(5):1146-1169.JB

Abstract

Acinetobacter baumannii, an opportunistic pathogen, has become multi-drug resistant (MDR) to major classes of antibacterial and poses grave threat to public health. The current study focused to screen novel phytotherapeutics against prioritised targets of Acinetobacter baumannii by computational investigation. Fourteen potential drug targets were screened based on their functional role in various biosynthetic pathways and the 3D structures of 9 targets were retrieved from Protein Data Bank and others were computationally predicted. By extensive literature survey, 104 molecules from 48 herbal sources were screened and subjected to virtual screening. Ten clinical isolates of A. baumannii were tested for antibiotic susceptibility towards clinafloxacin, imipenem and polymyxin-E. Computational screening suggested that Ajmalicine ((19α)-16, 17-didehydro-19-methyloxayohimban-16-carboxylic acid methyl ester from Rauwolfia serpentina), Strictamin (Akuammilan-17-oic acid methyl ester from Alstonia scholaris) and Limonin (7, 16-dioxo-7, 16-dideoxylimondiol from Citrus sps) exhibited promising binding towards multiple drug targets of A. baumannii in comparison with the binding between standard drugs and their targets. Limonin displayed promising binding potential (binding energy -9.8 kcal/mol) towards diaminopimelate epimerase (DapF) and UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA). Ajmalicine and Strictamin demonstrated good binding potential (-9.5, -8.5 kcal/mol, respectively) towards MurA and shikimate dehydrogenase (-7.8 kcal/mol). Molecular dynamic simulations further validated the docking results. In vitro assay suggested that the tested isolates exhibited resistance to clinafloxacin, imipenem and polymyxin-E and the herbal preparations (crude extract) demonstrated a significant antibacterial potential (p ≤ .05). The study suggests that the aforementioned lead candidates and targets can be used for structure-based drug screening towards MDR A. baumannii.

Authors+Show Affiliations

a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India. b Visvesvaraya Technological University , Belagavi , India.a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India. b Visvesvaraya Technological University , Belagavi , India.a Department of Biotechnology Engineering , Dayananda Sagar Institutions , Bengaluru 560 078 , Karnataka , India. b Visvesvaraya Technological University , Belagavi , India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29529934

Citation

Skariyachan, Sinosh, et al. "Screening of Potential Lead Molecules Against Prioritised Targets of multi-drug-resistant-Acinetobacter Baumannii - Insights From Molecular Docking, Molecular Dynamic Simulations and in Vitro Assays." Journal of Biomolecular Structure & Dynamics, vol. 37, no. 5, 2019, pp. 1146-1169.
Skariyachan S, Manjunath M, Bachappanavar N. Screening of potential lead molecules against prioritised targets of multi-drug-resistant-Acinetobacter baumannii - insights from molecular docking, molecular dynamic simulations and in vitro assays. J Biomol Struct Dyn. 2019;37(5):1146-1169.
Skariyachan, S., Manjunath, M., & Bachappanavar, N. (2019). Screening of potential lead molecules against prioritised targets of multi-drug-resistant-Acinetobacter baumannii - insights from molecular docking, molecular dynamic simulations and in vitro assays. Journal of Biomolecular Structure & Dynamics, 37(5), 1146-1169. https://doi.org/10.1080/07391102.2018.1451387
Skariyachan S, Manjunath M, Bachappanavar N. Screening of Potential Lead Molecules Against Prioritised Targets of multi-drug-resistant-Acinetobacter Baumannii - Insights From Molecular Docking, Molecular Dynamic Simulations and in Vitro Assays. J Biomol Struct Dyn. 2019;37(5):1146-1169. PubMed PMID: 29529934.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening of potential lead molecules against prioritised targets of multi-drug-resistant-Acinetobacter baumannii - insights from molecular docking, molecular dynamic simulations and in vitro assays. AU - Skariyachan,Sinosh, AU - Manjunath,Meghna, AU - Bachappanavar,Nikhil, Y1 - 2018/03/20/ PY - 2018/3/14/pubmed PY - 2020/4/10/medline PY - 2018/3/14/entrez KW - KW - Ajmalicine KW - DapF KW - Limonin KW - MurA KW - Strictamin KW - multi-drug resistant KW - novel phytotherapeutics KW - shikimate dehydrogenase SP - 1146 EP - 1169 JF - Journal of biomolecular structure & dynamics JO - J. Biomol. Struct. Dyn. VL - 37 IS - 5 N2 - Acinetobacter baumannii, an opportunistic pathogen, has become multi-drug resistant (MDR) to major classes of antibacterial and poses grave threat to public health. The current study focused to screen novel phytotherapeutics against prioritised targets of Acinetobacter baumannii by computational investigation. Fourteen potential drug targets were screened based on their functional role in various biosynthetic pathways and the 3D structures of 9 targets were retrieved from Protein Data Bank and others were computationally predicted. By extensive literature survey, 104 molecules from 48 herbal sources were screened and subjected to virtual screening. Ten clinical isolates of A. baumannii were tested for antibiotic susceptibility towards clinafloxacin, imipenem and polymyxin-E. Computational screening suggested that Ajmalicine ((19α)-16, 17-didehydro-19-methyloxayohimban-16-carboxylic acid methyl ester from Rauwolfia serpentina), Strictamin (Akuammilan-17-oic acid methyl ester from Alstonia scholaris) and Limonin (7, 16-dioxo-7, 16-dideoxylimondiol from Citrus sps) exhibited promising binding towards multiple drug targets of A. baumannii in comparison with the binding between standard drugs and their targets. Limonin displayed promising binding potential (binding energy -9.8 kcal/mol) towards diaminopimelate epimerase (DapF) and UDP-N-acetylglucosamine 1-carboxyvinyltransferase (MurA). Ajmalicine and Strictamin demonstrated good binding potential (-9.5, -8.5 kcal/mol, respectively) towards MurA and shikimate dehydrogenase (-7.8 kcal/mol). Molecular dynamic simulations further validated the docking results. In vitro assay suggested that the tested isolates exhibited resistance to clinafloxacin, imipenem and polymyxin-E and the herbal preparations (crude extract) demonstrated a significant antibacterial potential (p ≤ .05). The study suggests that the aforementioned lead candidates and targets can be used for structure-based drug screening towards MDR A. baumannii. SN - 1538-0254 UR - https://www.unboundmedicine.com/medline/citation/29529934/Screening_of_potential_lead_molecules_against_prioritised_targets_of_multi_drug_resistant_Acinetobacter_baumannii___insights_from_molecular_docking_molecular_dynamic_simulations_and_in_vitro_assays_ L2 - http://www.tandfonline.com/doi/full/10.1080/07391102.2018.1451387 DB - PRIME DP - Unbound Medicine ER -