Abstract
Malaria parasites show resistance to most of the antimalarial drugs and hence developing antimalarials which can act on multitargets rather than a single target will be a promising strategy of drug design. Here we report a new approach by which virtual screening of 292 unique phytochemicals present in 72 traditionally important herbs is used for finding out inhibitors of plasmepsin-2 and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings of the selected molecules by Random Forest algorithm model of Weka using the bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292 phytochemicals to be active against the targets. Toxtree scan cautioned 21 compounds to be either carcinogenic or mutagenic and were thus removed for further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as per the ‘rule of five’ criteria. Out of ten antimalarial drug targets, only two target proteins such as 3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The potential binding of the selected 46 compounds to the active sites of these four targets was analyzed using MOE software. The docked conformations and the interactions with the binding pocket residues of the target proteins were understood by ‘Ligplot’ analysis. It has been found that 8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies. Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone (Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking score.
Keywords: Malaria, Plasmodium falciparum, virtual screening, weka, ADME, molecular operating environment, molecular docking.
Combinatorial Chemistry & High Throughput Screening
Title:Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals
Volume: 19 Issue: 7
Author(s): Indira G. Shibi, Lilly Aswathy, Radhakrishnan S. Jisha, Vijay H. Masand and Jayant M. Gajbhiye
Affiliation:
Keywords: Malaria, Plasmodium falciparum, virtual screening, weka, ADME, molecular operating environment, molecular docking.
Abstract: Malaria parasites show resistance to most of the antimalarial drugs and hence developing antimalarials which can act on multitargets rather than a single target will be a promising strategy of drug design. Here we report a new approach by which virtual screening of 292 unique phytochemicals present in 72 traditionally important herbs is used for finding out inhibitors of plasmepsin-2 and falcipain-2 for antimalarial activity against P. falciparum. Initial screenings of the selected molecules by Random Forest algorithm model of Weka using the bioassay datasets AID 504850 and AID 2302 screened 120 out of the total 292 phytochemicals to be active against the targets. Toxtree scan cautioned 21 compounds to be either carcinogenic or mutagenic and were thus removed for further analysis. Out of the remaining 99 compounds, only 46 compounds offered drug-likeness as per the ‘rule of five’ criteria. Out of ten antimalarial drug targets, only two target proteins such as 3BPF and 3PNR of falcipain-2 and 1PFZ and 2BJU of plasmepsin-2 are selected as targets. The potential binding of the selected 46 compounds to the active sites of these four targets was analyzed using MOE software. The docked conformations and the interactions with the binding pocket residues of the target proteins were understood by ‘Ligplot’ analysis. It has been found that 8 compounds are dual inhibitors of falcipain-2 and plasmepsin-2, with the best binding energies. Compound 117 (6aR, 12aS)-12a-Hydroxy-9-methoxy-2,3-dimethylenedioxy-8-prenylrotenone (Usaratenoid C) present in the plant Millettia usaramensis showed maximum molecular docking score.
Export Options
About this article
Cite this article as:
Shibi G. Indira, Aswathy Lilly, Jisha S. Radhakrishnan, Masand H. Vijay and Gajbhiye M. Jayant, Virtual Screening Techniques to Probe the Antimalarial Activity of some Traditionally Used Phytochemicals, Combinatorial Chemistry & High Throughput Screening 2016; 19 (7) . https://dx.doi.org/10.2174/1386207319666160420141200
DOI https://dx.doi.org/10.2174/1386207319666160420141200 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Macrocyclic Hepatitis C Virus NS3/4A Protease Inhibitors: An Overview of Medicinal Chemistry
Current Medicinal Chemistry Subject Index to Volume 3
Current Drug Targets - CNS & Neurological Disorders Leuckart Synthesis and Pharmacological Assessment of Novel Acetamide Derivatives
Anti-Cancer Agents in Medicinal Chemistry Clinical Pharmacology of Serotonin Receptor Type 3 (5-HT3) Antagonists
Current Medicinal Chemistry - Central Nervous System Agents A Dig Deep to Scout the Pharmacological and Clinical Facet of Garlic (<i>Allium sativum</i>)
Current Traditional Medicine Action Mechanism of Antihistamines and the New Antihistamines
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents The Early Bird Catches the Worm – Can Evolution Teach us Lessons in Fighting HIV?
Current HIV Research Quinolone-Based Drugs Against Toxoplasma gondii and Plasmodium spp
Current Drug Targets - Infectious Disorders An Overview of Antiretroviral Agents for Treating HIV Infection in Paediatric Population
Current Medicinal Chemistry The Role of Ionotropic Glutamate Receptors in Childhood Neurodevelopmental Disorders: Autism Spectrum Disorders and Fragile X Syndrome
Current Neuropharmacology Brain Perfusion In Sepsis
Current Vascular Pharmacology Does Dysbiosis Increase the Risk of Developing Schizophrenia? - A Comprehensive Narrative Review
Current Topics in Medicinal Chemistry Epigenetic and Disease Targets by Polyphenols
Current Pharmaceutical Design Current Approaches for in vitro Drug Release Study of Long Acting Parenteral Formulations
Current Drug Delivery Viral Vectors for Cancer Gene Therapy: Viral Dissemination and Tumor Targeting
Current Gene Therapy Cellular and Subcellular Imaging in Live Mice Using Fluorescent Proteins
Current Pharmaceutical Biotechnology Sjogrens Syndrome and Lymphoma Development
Current Immunology Reviews (Discontinued) Shut-Down of Translation, a Global Neuronal Stress Response:Mechanisms and Pathological Relevance
Current Pharmaceutical Design Recent Developments in Drug Design of NO-donor Hybrid Compounds
Mini-Reviews in Medicinal Chemistry Modulation of Host Cell Nucleocytoplasmic Trafficking During Picornavirus Infection
Infectious Disorders - Drug Targets