scholarly journals Effect of Azadirachta indica Bio-Compounds against KpsM Protein of Acinetobacter baumannii

2021 ◽  
pp. 773-780
Author(s):  
V. Thiru Kumaran ◽  
A. S. Smiline Girija ◽  
P. P. Sankar Ganesh ◽  
J. Vijayashree Priyadharshini
Keyword(s):  
Binding Energy ◽  
Acinetobacter Baumannii ◽  
Azadirachta Indica ◽  
Nosocomial Infections ◽  
In Silico ◽  
Experimental Studies ◽  
Docking Simulation ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Selection Of

Background: Acinetobacter baumannii was considered as a low priority pathogen earlier, and is been now reported as a priority pathogen causing nosocomial infections. Selection of natural compounds to target the organism is the need of the hour. Aim: This study is aimed to target the KpsM protein of A. baumannii with the bio-compounds from Azadirachta indica using in-silico docking analysis. Materials and Methods: KpsM protein was retrieved and optimisation of protein was done. After that optimization and ligand preparation was carried out. It was continued by molinspiration assessment of the molecular properties of selected compounds. It was followed by docking simulation and docking visualisation. Results: Out of the 7 compounds of Azadirachta indica, dihydro diisoeugenol is the best compound to act on the KpsM protein of Acinetobacter baumannii and a binding energy of -6.83Kcal/Mol. Conclusion: The findings of the study reports isoeugenol with more binding energy than other compounds towards the selected protein KpsM of Acinetobacter baumannii. However it requires further experimental studies to understand the mechanism of its actions and safety.

scholarly journals ANTI-PARKINSON POTENTIAL OF PERSEA AMERICANA SEED EXTRACTS THROUGH IN-SILICO DOCKING STUDY

2020 ◽  
pp. 152-155
Author(s):  
RACHAEL EVANGELINE ◽  
NIHAL AHMED
Keyword(s):  
Binding Energy ◽  
Hydrogen Bonds ◽  
In Silico ◽  
Water Extract ◽  
Docking Study ◽  
Persea Americana ◽  
Ligand Docking ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Free Binding Energy

Objective: The aim of this study is to investigate the potential of Persea americana extracts for their Anti-Parkinson application through an in-silico docking study. Methods: PubChem and protein data bank databases were used to retrieve 3D structures. AutoDock4 was used to perform protein-ligand docking analysis. PyMOL was used to visualize the docking results. Results: Among the 30 ligand, the highest affinity was demonstrated by Hesperidin with a free binding energy of −6.8 kcal/mol and formation of five hydrogen bonds. The second highest significance was demonstrated by Biphenyl 4-(4-diethylaminobenzylidenamino) with a free binding energy of −5.9 kcal/mol with the formation of 2 hydrogen bonds. Among the three sets of phytochemicals from different solvent extracts, water extract demonstrated the highest potential as Anti-Parkinson active. Conclusion: P. americana extracts were analyzed for their Anti-Parkinson potential, and among the three extracts, the aqueous extract was predicted to have significant Anti-Parkinson potential, based on in silico docking analysis, due to the presence of active phytochemicals such as Hesperidin and others.

scholarly journals In Silico Screening of Sesquiterpene Lactones as Aldose Reductase Inhibitors

2021 ◽  
Vol 28 (2) ◽  
pp. 64-69
Author(s):  
A.M. Alhassan ◽  
I. Malami
Keyword(s):  
Molecular Docking ◽  
Binding Energy ◽  
Aldose Reductase ◽  
In Silico ◽  
Sesquiterpene Lactones ◽  
Docking Simulation ◽  
Binding Energies ◽  
In Silico Docking ◽  
Aldose Reductase Inhibitors ◽  
Reductase Inhibitors

Aldose reductase, a key enzyme of the polyol pathway catalyses NADPH-dependent reduction of glucose to sorbitol. Increased activity of this enzyme is considered a major factor contributing to the development of diabetic complications hence could be an important target in the treatment of these complications. In this work, a database of sesquiterpenes was prepared and screened for their drug-like properties based on the Lipinski’s rule of 5. The co-crystallised structure of aldose reductase was obtained from the Protein Databank and prepared for docking. In silico docking experiments was performed on Autodock tools using 198 sesquiterpene lactones that passed screening, and compounds with the lowest binding energy and favourable binding interactions were selected for molecular docking simulation. Six of the best ranking compounds selected had binding energies ranging from–11.96 Kcal/mol to -9.45 Kcal/mol  and were comparable to the energy of the standard inhibitor Idd594 used in the study. They also show good complementarity in their binding to the residues of the binding pocket. The results suggest that dehydrooopodin (1), 11(S),13-dihydrolactucopicrin (2), and Chrysanin (3) offered potential inhibitory activities toward aldose reductase and may serve as lead compounds for in vivo validation as aldose reductase inhibitors. Keywords: Sesquiterpene lactones, Aldose reductase, Binding energy, Molecular docking, Autodock

In vitro and in vivo activities of imipenem combined with BLI-489 against class D β-lactamase-producing Acinetobacter baumannii

2020 ◽  
Author(s):  
Yung-Chih Wang ◽  
Shu-Wei Huang ◽  
Ming-Hsien Chiang ◽  
I-Ming Lee ◽  
Shu-Chen Kuo ◽  
...  
Keyword(s):  
Acinetobacter Baumannii ◽  
In Silico ◽  
Active Sites ◽  
Synergistic Effects ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Class D ◽  
Time Kill

Abstract Background According to our preliminary study, BLI-489 has the potential to inhibit the hydrolysing activity of OXA-51-like β-lactamase produced by carbapenem-resistant Acinetobacter baumannii (CRAb). Objectives In the present study, the in vitro and in vivo activities of imipenem combined with BLI-489 against CRAb producing carbapenem-hydrolysing class D β-lactamases (CHDLs), namely OXA-23, OXA-24, OXA-51 and OXA-58, were determined. Methods A chequerboard analysis of imipenem and BLI-489 was performed using 57 and 7 clinical CRAb isolates producing different CHDLs and MBLs, respectively. Four representative strains harbouring different CHDL genes were subjected to a time–kill assay to evaluate the synergistic effects. An in silico docking analysis was conducted to simulate the interactions between BLI-489 and the different families of CHDLs. The in vivo activities of this combination were assessed using a Caenorhabditis elegans survival assay and a mouse pneumonia model. Results Chequerboard analysis showed that imipenem and BLI-489 had a synergistic effect on 14.3, 92.9, 100, 16.7 and 100% of MBL-, OXA-23-, OXA-24-like-, OXA-51-like- and OXA-58-producing CRAb isolates, respectively. In the time–kill assay, imipenem and BLI-489 showed synergy against OXA-24-like-, OXA-51-like- and OXA-58-, but not OXA-23-producing CRAb isolates after 24 h. The in silico docking analysis showed that BLI-489 could bind to the active sites of OXA-24 and OXA-58 to confer strong inhibition activity. The combination of imipenem and BLI-489 exhibited synergistic effects for the rescue of CRAb-infected C. elegans and mice. Conclusions Imipenem combined with BLI-489 has synergistic effects against CHDL-producing CRAb isolates.

scholarly journals In vitro toxicity and in silico docking analysis of two novel selective AH-receptor modulators

2018 ◽  
Vol 52 ◽  
pp. 178-188 ◽  
Author(s):  
Selma Mahiout ◽  
Sara Giani Tagliabue ◽  
Atefeh Nasri ◽  
Iyekhoetin Matthew Omoruyi ◽  
Lars Pettersson ◽  
...  
Keyword(s):  
In Silico ◽  
In Vitro Toxicity ◽  
Ah Receptor ◽  
Docking Analysis ◽  
In Silico Docking ◽  
Receptor Modulators

scholarly journals Development of a Novel In Silico Docking Simulation Model for the Fine HIV-1 Cytotoxic T Lymphocyte Epitope Mapping

PLoS ONE ◽  
2012 ◽  
Vol 7 (7) ◽  
pp. e41703 ◽  
Author(s):  
Masahiko Mori ◽  
Kei Matsuki ◽  
Tomoyuki Maekawa ◽  
Mari Tanaka ◽  
Busarawan Sriwanthana ◽  
...  
Keyword(s):  
Simulation Model ◽  
T Lymphocyte ◽  
In Silico ◽  
Epitope Mapping ◽  
Cytotoxic T Lymphocyte ◽  
Docking Simulation ◽  
In Silico Docking ◽  
Hiv 1

scholarly journals Selection of the Optimal L-asparaginase II Against Acute Lymphoblastic Leukemia: An In Silico Approach

JMIRx Med ◽  
10.2196/29844 ◽  
2021 ◽  
Vol 2 (3) ◽  
pp. e29844 ◽  
Author(s):  
Adesh Baral ◽  
Ritesh Gorkhali ◽  
Amit Basnet ◽  
Shubham Koirala ◽  
Hitesh Kumar Bhattarai
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Binding Energy ◽  
Cancer Cells ◽  
In Silico ◽  
Lymphoblastic Leukemia ◽  
Streptomyces Griseus ◽  
Homologous Proteins ◽  
E Coli ◽  
Streptomyces Collinus ◽  
Selection Of

Background L-asparaginase II (asnB), a periplasmic protein commercially extracted from E coli and Erwinia, is often used to treat acute lymphoblastic leukemia. L-asparaginase is an enzyme that converts L-asparagine to aspartic acid and ammonia. Cancer cells are dependent on asparagine from other sources for growth, and when these cells are deprived of asparagine by the action of the enzyme, the cancer cells selectively die. Objective Questions remain as to whether asnB from E coli and Erwinia is the best asparaginase as they have many side effects. asnBs with the lowest Michaelis constant (Km; most potent) and lowest immunogenicity are considered the most optimal enzymes. In this paper, we have attempted the development of a method to screen for optimal enzymes that are better than commercially available enzymes. Methods In this paper, the asnB sequence of E coli was used to search for homologous proteins in different bacterial and archaeal phyla, and a maximum likelihood phylogenetic tree was constructed. The sequences that are most distant from E coli and Erwinia were considered the best candidates in terms of immunogenicity and were chosen for further processing. The structures of these proteins were built by homology modeling, and asparagine was docked with these proteins to calculate the binding energy. Results asnBs from Streptomyces griseus, Streptomyces venezuelae, and Streptomyces collinus were found to have the highest binding energy (–5.3 kcal/mol, –5.2 kcal/mol, and –5.3 kcal/mol, respectively; higher than the E coli and Erwinia asnBs) and were predicted to have the lowest Kms, as we found that there is an inverse relationship between binding energy and Km. Besides predicting the most optimal asparaginase, this technique can also be used to predict the most optimal enzymes where the substrate is known and the structure of one of the homologs is solved. Conclusions We have devised an in silico method to predict the enzyme kinetics from a sequence of an enzyme along with being able to screen for optimal alternative asnBs against acute lymphoblastic leukemia.

scholarly journals In vivo and in silico Evaluation of Analgesic and Hypoglycemic Activities of Roots of Acacia nilotica, Azadirachta indica and Justica adhatoda

2021 ◽  
Vol 20 (2) ◽  
pp. 185-197
Author(s):  
Fahad Hussain ◽  
Poushali Saha ◽  
Fahad Imtiaz Rahman ◽  
Mohammad Salim Hossain ◽  
SM Abdur Rahman
Keyword(s):  
Blood Glucose ◽  
Binding Energy ◽  
Azadirachta Indica ◽  
Oral Bioavailability ◽  
In Silico ◽  
Diclofenac Sodium ◽  
Acacia Nilotica ◽  
Specific Chemical ◽  
Root Extracts ◽  
Methanol Extracts

The present study focuses on the investigation of methanol extracts of roots of three indigenous plants of Bangladesh namely Acacia nilotica, Azadirachta indica and Justicia adhatoda to evaluate their analgesic and hypoglycemic activities in experimental animal model along with in silico modelling of several compounds present in the root extracts of these plants. Analgesic and hypoglycemic activities were evaluated in Swiss albino mice using acetic acid-induced writhing inhibition method and glucose tolerance test, respectively. In silico molecular docking and ADME study was conducted to assess the binding affinity with the target receptors and oral bioavailability of the compounds. The methanol extracts of A. nilotica, J. adhatoda and A. indica roots at a dose of 400 mg/kg body weight reduced the number of writhes by 61.53%, 54.61% and 47.69%, respectively compared to standard diclofenac sodium (70.77% at a dose of 50 mg/kg bw) (p<0.05). A. nilotica and A. indica root extracts showed significant hypoglycemic activity at a dose of 400 mg/kg bw (% reduction of blood glucose 43.66 and 37.55% respectively, p<0.001) and J. adhatoda root extract reduced the blood glucose level by 33.71% (p<0.001) compared to that of standard drug, glibenclamide (57.46% reduction of blood glucose) after 120 minutes of administration. Among the computationally tested compounds, flavan-3-ol showed the lowest binding energy (-8.7 kcal/mol) with both COX-1 and COX-2 compared to standard diclofenac sodium (-7.8 kcal/mol). On the other hand, quercetin demonstrated the lowest binding energy (-8.8 kcal/mol) with ATP-sensitive potassium channel with Sulfonylurea Receptor 1 subunit among the tested compounds compared to standard glibenclamide (-9.3 kcal/mol). All the compounds showed high oral bioavailability in ADME analysis. Among all the root extracts, A. nilotica exhibited the most promising analgesic and hypoglycemic activities and should be employed to future investigation for isolating specific chemical constituents. Dhaka Univ. J. Pharm. Sci. 20(2): 185-197, 2021 (December)

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