Abstract
Background: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy.
Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain.
Materials & Methods: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.
Results: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies.
Conclusion: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.
Keywords: Pyrazole, Plasmodium falciparum, antimalarial, Falcipain-2, docking, ADME.
Combinatorial Chemistry & High Throughput Screening
Title:Pyrazole Schiff Base Hybrids as Anti-Malarial Agents: Synthesis, In Vitro Screening and Computational Study
Volume: 21 Issue: 3
Author(s): Shilpy Aggarwal, Deepika Paliwal, Dhirender Kaushik, Girish Kumar Gupta and Ajay Kumar*
Affiliation:
- Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119,India
Keywords: Pyrazole, Plasmodium falciparum, antimalarial, Falcipain-2, docking, ADME.
Abstract: Background: Malaria is one of the most vital infectious diseases caused by protozoan parasites of the Plasmodium genus. As P. falciparum, the cause of most of the severe cases of malaria, is increasingly resistant to available drugs such as amodioquine, chloroquine, artemisinin, and antifolates, there is an urgent need to identify new targets for chemotherapy.
Objective: This study screened novel pyrazole derivatives carrying iminium & benzothiazole group for antimalarial potential against P. falciparum chloroquine sensitive (3D7) strain.
Materials & Methods: Several pyrazole schiff base hybrids with a wide range of substitution have been synthesized via condensation of substituted aniline with substituted 4-formylpyrazole and evaluated for their in vitro antimalarial activity against asexual blood stages of human malaria parasite, Plasmodium falciparum. The interaction of these conjugate hybrids was also investigated by molecular docking studies in the binding site of P. falciparum cystein protease falcipain-2. The pharmacokinetic properties were also studied using ADME prediction.
Results: Among all compounds, 6bf and 6bd were found to be potential molecules with EC50 1.95µg/ml and 1.98µg/ml respectively. Docking study results reveal that the pyrazole schiff base derivatives occupy the PfFP binding sites and they show good interactions with significant values of binding energies.
Conclusion: We provide evidence which implicates pyrazole Schiff base hybrids as potential prototypes for the development of antimalarial agents.
Export Options
About this article
Cite this article as:
Aggarwal Shilpy , Paliwal Deepika , Kaushik Dhirender , Gupta Kumar Girish and Kumar Ajay *, Pyrazole Schiff Base Hybrids as Anti-Malarial Agents: Synthesis, In Vitro Screening and Computational Study, Combinatorial Chemistry & High Throughput Screening 2018; 21 (3) . https://dx.doi.org/10.2174/1386207321666180213092911
DOI https://dx.doi.org/10.2174/1386207321666180213092911 |
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
-
A Tutorial and Performance Analysis on ENVI Tools for SAR Image Despeckling
Current Signal Transduction Therapy Multifunctional Nanomedicine Platform for Cancer Specific Delivery of siRNA by Superparamagnetic Iron Oxide Nanoparticles-Dendrimer Complexes
Current Drug Delivery Recent Advances in Antiviral Activity of Benzo/Heterothiadiazine Dioxide Derivatives
Current Medicinal Chemistry Synthesis and In Vitro Antitumor Activity of Novel Fluorine Containing Pyrazoles and Pyrazolines
Letters in Drug Design & Discovery MMP-2 Selectivity in Hydroxamate-Type Inhibitors
Current Medicinal Chemistry The Mechanistic Target of Rapamycin (mTOR): Novel Considerations as an Antiviral Treatment
Current Neurovascular Research Distorted Key Theory and its Implication for Drug Development
Current Proteomics Asymmetric 1,3-Dipolar Cycloaddition of Chiral α, β-Unsaturated-γ-Sultams with Nitrile Oxides and Nitrones
Letters in Organic Chemistry The Synthesis, Structure and Activity Evaluation of Secnidazole Derivatives as Helicobacter pylori Urease Inhibitors
Current Bioactive Compounds Natural Compounds for Overcoming Multidrug Resistance in Mycobacteria
Recent Patents on Biotechnology Anticancer Potential of Dietary Natural Products: A Comprehensive Review
Anti-Cancer Agents in Medicinal Chemistry Patenting Human Genes and Stem Cells
Recent Patents on DNA & Gene Sequences Editorial [Extravascular Lung Water Measurements: Dont Jump Off the Bandwagon Yet! ]
Current Respiratory Medicine Reviews Development of Sodium-Dependent Glucose Co-Transporter 2 Inhibitors as Potential Anti-Diabetic Therapeutics
Current Topics in Medicinal Chemistry COVID-19, Angiotensin-Converting Enzyme 2 and Renin-Angiotensin System Inhibition: Implications for Practice
Current Hypertension Reviews What we have Learned from Animal Models of Mycoplasma pneumoniae Disease: Virulence Mechanisms and Host Responses
Current Pediatric Reviews COVID-19 Related Coagulopathy: What is Known Up to Now
Current Medicinal Chemistry Natural Products with Tandem Anti-inflammatory, Immunomodulatory and Anti-SARS-CoV/2 Effects: A Drug Discovery Perspective against SARS-CoV-2
Current Medicinal Chemistry Noninvasive Mechanical Ventilation in the Treatment of Community-Acquired Pneumonia
Current Respiratory Medicine Reviews Standards and Novel Therapeutic Options in the Treatment of Patients with Soft Tissue Sarcoma
Reviews on Recent Clinical Trials