Molecular Insights into the Interaction of Ursolic Acid and Cucurbitacin from Colocynth with Therapeutic Targets of Mycobacterium tuberculosis

2020 ◽  
Vol 17 (10) ◽  
pp. 1309-1318
Author(s):  
Mohammad Ajmal Ali ◽  
Mohammad Abul Farah ◽  
Joongku Lee ◽  
Khalid M. Al-Anazi ◽  
Fahad M.A. Al-Hemaid
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Ursolic Acid ◽  
Causes Of Death ◽  
Simulation Studies ◽  
Autodock Vina ◽  
Docking Analysis ◽  
Target Proteins ◽  
Target Drug ◽  
File Formats ◽  
Cucurbitacin E

Aims: Medicinal plants like Citrullus colocynthis are a potential choice to produce helpful novel antimycobacterial drugs. The existence of a range of natural products in the plants, especially Ursolic Acid (UA) and cucurbitacin E 2-0-β-d-glucopyranoside (CEG), with promising antibacterial activity against a variety of bacteria, prompted the need to check its actions against Mycobacterium tuberculosis (Mtb). Background: Mycobacterium tuberculosis (Mtb), an obligate human pathogen causes tuberculosis and is one of the major causes of death worldwide. A few combinations of drugs are currently accessible for treating TB patients, but these are inadequate to tackle worldwide TB cases. Objective: The molecular interactions between ursolic acid and cucurbitacin E with the eight potential Mtb target proteins were investigated with the objective of finding drug-like inhibitors. Methods: Avogadro v.1.2.0 and Openbabel v.2.4.1 were used for creating file formats required for docking analysis. Molecular docking was performed with eight different proteins essential for Mtb metabolism and survival. AutoDock v.4.2 and AutoDock vina v.1.1.2 were used for docking and Gromacs 5.1.4 was used for simulation studies. Results and Discussion: Among the two ligands used in this research, cucurbitacin E showed a better docking score relative to the drugs presently available for all the target proteins. Rifampicin showed the best binding affinity (among known inhibitors) i.e. -10.8 kcal/mol with C terminal caspase recruitment domain. Moreover, ursolic acid and cucurbitacin E showed uniform binding score (above -7.5 kcal/mol) with all the target proteins, acknowledged its availability as a potential multi-target drug. Conclusion: Ursolic acid can be useful in the creation of novel, multi-targeted and effective anti- TB medicines since it showed stable structure with FabH.

scholarly journals Molecular modelling and simulation studies of the Mycobacterium tuberculosis multidrug efflux pump protein Rv1258c

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0207605 ◽  
Author(s):  
Ruben Cloete ◽  
Erika Kapp ◽  
Jacques Joubert ◽  
Alan Christoffels ◽  
Sarel F. Malan
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Molecular Modelling ◽  
Efflux Pump ◽  
Modelling And Simulation ◽  
Simulation Studies ◽  
Multidrug Efflux ◽  
Multidrug Efflux Pump

scholarly journals Update on TB Vaccine Pipeline

2020 ◽  
Vol 10 (7) ◽  
pp. 2632 ◽  
Author(s):  
Carlos Martin ◽  
Nacho Aguilo ◽  
Dessislava Marinova ◽  
Jesus Gonzalo-Asensio
Keyword(s):  
Drug Resistance ◽  
Clinical Trials ◽  
Mycobacterium Tuberculosis ◽  
Infectious Diseases ◽  
Significant Role ◽  
Causes Of Death ◽  
Multi Drug Resistance ◽  
Bacillus Calmette Guerin ◽  
The World

In addition to antibiotics, vaccination is considered among the most efficacious methods in the control and the potential eradication of infectious diseases. New safe and effective vaccines against tuberculosis (TB) could be a very important tool and are called to play a significant role in the fight against TB resistant to antimicrobials. Despite the extended use of the current TB vaccine Bacillus Calmette-Guérin (BCG), TB continues to be transmitted actively and continues to be one of the 10 most important causes of death in the world. In the last 20 years, different TB vaccines have entered clinical trials. In this paper, we review the current use of BCG and the diversity of vaccines in clinical trials and their possible indications. New TB vaccines capable of protecting against respiratory forms of the disease caused by sensitive or resistant Mycobacterium tuberculosis strains would be extremely useful tools helping to prevent the emergence of multi-drug resistance.

In vitro effect of ursolic acid on the inhibition of Mycobacterium tuberculosis and its cell wall mycolic acid

2015 ◽  
Vol 33 ◽  
pp. 17-24 ◽  
Author(s):  
Md. Anirban Jyoti ◽  
Tamanna Zerin ◽  
Tae-Hyun Kim ◽  
Tae-Seon Hwang ◽  
Woong Sik Jang ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Ursolic Acid ◽  
Mycolic Acid ◽  
Vitro Effect

Molecular docking and molecular dynamics studies on β-lactamases and penicillin binding proteins

2014 ◽  
Vol 10 (4) ◽  
pp. 891-900 ◽  
Author(s):  
K. M. Kumar ◽  
Anand Anbarasu ◽  
Sudha Ramaiah
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
High Stability ◽  
Binding Proteins ◽  
Simulation Studies ◽  
Docking Analysis ◽  
Penicillin Binding Proteins ◽  
The Stability ◽  
Molecular Docking Analysis

Molecular docking analysis of β-lactam antibiotics was performed with PBP2a, PBP2b, PBP2x and SHV-1 proteins, and the best interaction is observed between Ceftobiprole and the PBP2x complex; furthermore the stability of the complex is confirmed using simulation studies; our results show that the Ceftobiprole–PBP2x complex shows high stability as evident by RMSD,Rgand H-bonds.

scholarly journals Difficult Diseases: Tuberculosis and Other Infections

2020 ◽  
pp. 213-237
Author(s):  
Claire Hilton
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Infectious Diseases ◽  
Death Rate ◽  
Causes Of Death ◽  
Community Dwelling ◽  
Hand Washing ◽  
Duty Of Care ◽  
Open Wards ◽  
As If

Abstract The pre-war annual asylum death rate of under ten per cent rose to 12 per cent in 1915–1916, and 20 per cent in 1918. There was little alarm, because causes of death were the same as pre-war, often infectious diseases, so it did not indicate staff failing in their duty of care, such as if the rise been attributed to “accidents” or suicide. Little was done to stem the rising death rate. A parallel rise did not occur in community dwelling civilians. Numerous practices, known to be unhygienic, risked spreading infection. They included: treating healthy and infectious patients together in open wards; lack of hand washing by laundry and kitchen workers and by patients after using the lavatory; lack of measures to prevent inhalation of mycobacterium tuberculosis; and drying soiled underclothing in the ward to be worn again without washing. Overcrowding, understaffing and war time austerity aggravated the situation.

scholarly journals Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

2021 ◽  
Author(s):  
Govinda Rao Dabburu ◽  
Manish Kumar ◽  
Naidu Subbarao
Keyword(s):  
Plasmodium Falciparum ◽  
Molecular Docking ◽  
Drug Target ◽  
Docking Studies ◽  
Simulation Studies ◽  
Docking Analysis ◽  
Discovery Studio ◽  
Potential Inhibitors ◽  
Key Words Malaria ◽  
Leucyl Aminopeptidase

Abstract: Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP. Key words: Malaria, M17 Leucyl Aminopeptidase, ADMET, X-SCORE

scholarly journals Molecular Docking, Dynamics Simulation, and Scanning Electron Microscopy (SEM) Examination of Clinically Isolated Mycobacterium tuberculosis by Ursolic Acid: A Pentacyclic Triterpenes

2019 ◽  
Vol 19 (2) ◽  
pp. 328
Author(s):  
Dian Ayu Eka Pitaloka ◽  
Sophi Damayanti ◽  
Aluicia Anita Artarini ◽  
Elin Yulinah Sukandar
Keyword(s):  
Electron Microscopy ◽  
Molecular Dynamics ◽  
Scanning Electron Microscopy ◽  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Ursolic Acid ◽  
Resistant Strain ◽  
Dynamics Simulation ◽  
Computational Docking ◽  
Scanning Electron

The purpose of this study was to analyze the inhibitory action of ursolic acid (UA) as an antitubercular agent by computational docking studies and molecular dynamics simulations. The effect of UA on the cell wall of Mycobacterium tuberculosis (MTB) was evaluated by using Scanning Electron Microscopy (SEM). UA was used as a ligand for molecular interaction and investigate its binding activities to a group of proteins involved in the growth of MTB and the biosynthesis of the cell wall. Computational docking analysis was performed by using autodock 4.2.6 based on scoring functions. UA binding was confirmed by 30 ns molecular dynamics simulation using gromacs 5.1.1. H37Rv sensitive strain and isoniazid-resistant strain were used in the SEM study. UA showed to have the optimum binding affinity to inhA (Two-trans-enoyl-ACP reductase enzyme involved in elongation of fatty acid) with the binding energy of -9.2 kcal/mol. The dynamic simulation showed that the UA-inhA complex relatively stable and found to establish hydrogen bond with Thr196 and Ile194. SEM analysis confirms that UA treatment in both sensitive strain and resistant strain affected the morphology cell wall of MTB. This result indicated that UA could be one of the potential ligands for the development of new antituberculosis drugs.

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