scholarly journals Computational Studies of Drug Repurposing Targeting P-Glycoprotein-Mediated Multidrug-Resistance Phenotypes in Agents of Neglected Tropical Diseases

2020 ◽  
Author(s):  
Nivedita Jaishankar ◽  
Sangeetha Muthamilselvan ◽  
Ashok Palaniappan
Keyword(s):  
Multidrug Resistance ◽  
Neglected Tropical Diseases ◽  
Drug Repurposing ◽  
Computational Studies ◽  
Tropical Diseases ◽  
P Glycoprotein

scholarly journals Computational studies of drug repurposing targeting P-glycoprotein mediated multidrug-resistance phenotypes in agents of neglected tropical diseases

2020 ◽  
Author(s):  
Nivedita Jaishankar ◽  
Sangeetha Muthamilselvan ◽  
Ashok Palaniappan
Keyword(s):  
Multidrug Resistance ◽  
Leishmania Major ◽  
Nearest Neighbor ◽  
Efflux Pump ◽  
Neglected Tropical Diseases ◽  
New Drugs ◽  
List Type ◽  
Tropical Diseases ◽  
P Glycoprotein ◽  
Query Coverage

ABSTRACTMammalian ABCB1 P-glycoprotein is an ATP- dependent efflux pump with broad substrate specificity associated with cellular drug resistance. Homologous to this role in mammalian biology, the P-glycoprotein of agents of neglected tropical diseases (NTDs) mediates the emergence of multidrug-resistance phenotypes. The clinical and socioeconomic implications of NTDs are exacerbated by the lack of research interest among Big Pharma for treating such conditions. This work aims to characterise P-gp homologues in certain agents of key NTDs, namely Protozoa: Leishmania major, Trypanosoma cruzi;Helminths: Onchocerca volvulus, Schistosoma mansoni.PSI-BLAST searches against the genome of each of these organisms confirmed the presence of P-gp homologues. Each homologue was aligned against five P-gp sequences of known structure, to identify the most suitable template based on sequence homology, phylogenetic nearest neighbor, and query coverage. Antibiotics used in the current line of therapy against each of these pathogens were identified using PubChem and their SMILES structures were converted to PDB using BABEL software. Potential antibiotics to test against the set of FDA-approved antibiotics were identified based on similarity to the chemical class of the known drugs and repurposing of the existing drugs. Docking studies of the respective modelled Pgp structures and the set of antibiotic ligands were carried out using AutoDock and the most tenable target-ligand conformations were assessed. The interacting residues within 4.5 Å of the ligand were identified, and the binding pockets were studied. The relative efficacy of the new drugs and the interacting pump residues were identified. Our studies could lay the foundation for the development of effective synergistic or new therapies against key neglected tropical diseases.

THE ROLE OF EBM AND CLINICAL PRACTICE GUIDELINES IN GENERATING RESEARCH AND INTERVENTIONS IN NEGLECTED TROPICAL DISEASES: A RATIONAL MODEL FOR DEVELOPING COUNTRIES

2020 ◽  
Author(s):  
Cristhian David Morales-Plaza
Keyword(s):  
Developing Countries ◽  
Clinical Practice ◽  
Clinical Practice Guidelines ◽  
Practice Guidelines ◽  
Neglected Tropical Diseases ◽  
Tropical Diseases ◽  
Rational Model ◽  
Clinical Practices ◽  
Vulnerable Communities

Guarantee better clinical practices among clinicians who attend NTDs in developing countries as well as provide education in vector control in hotspot vulnerable communities

Transfection with Protein Kinase Cα Confers Increased Multidrug Resistance to MCF-7 Cells Expressing P-Glycoprotein

1991 ◽  
Vol 3 (6) ◽  
pp. 181-189 ◽  
Author(s):  
Gang Yu ◽  
Shakeel Ahmad ◽  
Angelo Aquino ◽  
Craig R. Fairchild ◽  
Jane B. Trepel ◽  
...  
Keyword(s):  
Multidrug Resistance ◽  
Protein Kinase ◽  
P Glycoprotein ◽  
Protein Kinase Cα ◽  
Mcf 7

Role of ABCB5 P-Glycoprotein in Breast Cancer Multidrug Resistance

2005 ◽  
Author(s):  
Markus H. Frank
Keyword(s):  
Breast Cancer ◽  
Multidrug Resistance ◽  
P Glycoprotein

Heterocycles in the Treatment of Neglected Tropical Diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Kush K. Maheshwari ◽  
Debasish Bandyopadhyay
Keyword(s):  
Developing Countries ◽  
Heterocyclic Compounds ◽  
Neglected Tropical Diseases ◽  
World Health ◽  
Current Status ◽  
Poor People ◽  
Tropical Diseases ◽  
Concise Review ◽  
The World ◽  
Health Organization

Background: Neglected tropical diseases (NTDs) affect a huge population of the world and majority of the victims belong to the poor community of the developing countries. Until now, the World Health Organization (WHO) has identified 20 tropical diseases as NTDs that must be addressed with high priority. However, many heterocyclic scaffolds have demonstrated potent therapeutic activity against several NTDs. Objective: There are three major objectives: (1) To discuss the causes, symptoms, and current status of all the 20 NTDs; (2) To explore the available heterocyclic drugs, and their mechanism of actions (if known) that are being used to treat NTDs; (3) To develop general awareness on NTDs among the medicinal/health research community and beyond. Methods: The 20 NTDs have been discussed according to their alphabetic orders along with the possible heterocyclic remedies. Current status of treatment with an emphasis on the heterocyclic drugs (commercially available and investigational) has been outlined. In addition, brief discussion of the impacts of NTDs on socio-economic condition is included. Results: NTDs are often difficult to diagnose and the problem is worsened by the unhealthy hygiene, improper awareness, and inadequate healthcare in the developing countries where these diseases primarily affect poor people. The statistics include duration of suffering, numbers affected, and access to healthcare and medication. The mechanism of actions of various heterocyclic drugs, if reported, have been briefly summarized. Conclusion: Scientists and pharmaceutical corporations should allocate more resources to reveal the in-depth mechanism of actions of many heterocyclic drugs that are currently being used for the treatment of NTDs. Analysis of current heterocyclic compounds and development of new medications can help in the fight to reduce/remove the devastating effects of NTDs. An opinion-based concise review has been presented. Based on available literature, this is the first effect to present all the 20 NTDs and related heterocyclic compounds under the same umbrella.

Combating P-glycoprotein-Mediated Multidrug Resistance Using Therapeutic Nanoparticles

2013 ◽  
Vol 19 (37) ◽  
pp. 6655-6666 ◽  
Author(s):  
Qiu Zhang ◽  
Fei Li
Keyword(s):  
Multidrug Resistance ◽  
P Glycoprotein
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