Abstract
Leflunomide is an immunomodulating drug that has been used clinically for the treatment of rheumatoid arthritis and other immune system disorders. As a continuation of our previous work, four novel analogues of leflunomide (6a, 6b, 7a and 7b) were synthesized; here, an imidazolyl group has replaced the isoxazolyl moiety, while the 4- trifluoromethylphenyl group has been retained. These analogues were synthesized and investigated in vitro for their immunomodulating activity by examining human lymphocyte proliferation and determining the cytokine interferon-γ concentrations in human lymphocyte cells. For this purpose, 5 x 104 human lymphocyte cells were incubated at 37°C in 5% CO2 with phytohemagglutinin and one of the analogues (concentrations ranging from 1 to 100 mM), negative controls or cyclosporine (0.1 mM). The compounds’ effects on lymphocyte proliferation and interferon-γ (IFN-γ) production were determined using an MTT assay and an ELISA, respectively. All compounds were found to have significant effects on both lymphocyte proliferation and IFN-γ production in comparison to the negative control. However, the compounds’ effects were weaker than those of the positive control. Some differences among compounds 6a, 6b, 7a and 7b were seen on lymphocyte proliferation and cytokine production. Compound 6a (R=CH3 containing a trifluoromethylaniline moiety) suppressed lymphocyte proliferation and IFN-γ production with a potency comparable to the positive control. Therefore, further studies to evaluate the compound’s effects in clinical conditions are suggested.
Keywords: Leflunomide, Immunomodulation, Interferon-γ, MTT assay, Drug synthesis, phytohemagglutinin, cytokine, immunosuppressive, spectrophotometer, acetonitrile
Medicinal Chemistry
Title:Synthesis and Immunomodulation of Human Lymphocyte Proliferation and Cytokine (Interferon-γ) Production of Four Novel Leflunomide Analogues
Volume: 8 Issue: 5
Author(s): Seyed Adel Moalem, Farzin Hadizadeh, Elham Saber Farimani, Maryam Rameshrad and Maryam Allahyari
Affiliation:
Keywords: Leflunomide, Immunomodulation, Interferon-γ, MTT assay, Drug synthesis, phytohemagglutinin, cytokine, immunosuppressive, spectrophotometer, acetonitrile
Abstract: Leflunomide is an immunomodulating drug that has been used clinically for the treatment of rheumatoid arthritis and other immune system disorders. As a continuation of our previous work, four novel analogues of leflunomide (6a, 6b, 7a and 7b) were synthesized; here, an imidazolyl group has replaced the isoxazolyl moiety, while the 4- trifluoromethylphenyl group has been retained. These analogues were synthesized and investigated in vitro for their immunomodulating activity by examining human lymphocyte proliferation and determining the cytokine interferon-γ concentrations in human lymphocyte cells. For this purpose, 5 x 104 human lymphocyte cells were incubated at 37°C in 5% CO2 with phytohemagglutinin and one of the analogues (concentrations ranging from 1 to 100 mM), negative controls or cyclosporine (0.1 mM). The compounds’ effects on lymphocyte proliferation and interferon-γ (IFN-γ) production were determined using an MTT assay and an ELISA, respectively. All compounds were found to have significant effects on both lymphocyte proliferation and IFN-γ production in comparison to the negative control. However, the compounds’ effects were weaker than those of the positive control. Some differences among compounds 6a, 6b, 7a and 7b were seen on lymphocyte proliferation and cytokine production. Compound 6a (R=CH3 containing a trifluoromethylaniline moiety) suppressed lymphocyte proliferation and IFN-γ production with a potency comparable to the positive control. Therefore, further studies to evaluate the compound’s effects in clinical conditions are suggested.
Export Options
About this article
Cite this article as:
Adel Moalem Seyed, Hadizadeh Farzin, Saber Farimani Elham, Rameshrad Maryam and Allahyari Maryam, Synthesis and Immunomodulation of Human Lymphocyte Proliferation and Cytokine (Interferon-γ) Production of Four Novel Leflunomide Analogues, Medicinal Chemistry 2012; 8 (5) . https://dx.doi.org/10.2174/157340612802084180
DOI https://dx.doi.org/10.2174/157340612802084180 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
Carbohydrates in Computational and Medicinal Chemistry
Carbohydrates are the most essential organic molecules and are involved in the maintenance of various physiological and metabolic processes in living organisms. Carbohydrate-based compounds have come to the attention of researchers because of their significant contributions to biological functions, such as cell development and cell proliferation, connections between several cells, ...read more
Recent Advances in the Medicinal Chemistry of Cancer
Scope of the Thematic Issue: Correlation between structure and function is one of the important aspects of the success of anti-cancer compounds associated with their structure-activity interactions, physiology, biochemical, molecular, and genetic processes. Overcoming these obstacles is key to obtaining further insights into developments in rational drug design, bioorganic chemistry, ...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
-
Obesity in the Childhood: A Link to Adult Hypertension
Current Pharmaceutical Design Biomedical Applications of Protein Microarrays
Current Medicinal Chemistry Systematic Review of the Role of Microparticles in Systemic Sclerosis
Current Rheumatology Reviews Evaluation of Topical Gels Containing Ketorolac Tromethamine on Inflammation and Hyperalgesia in Rats
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Subject Index To Volume 1
Recent Patents on Anti-Cancer Drug Discovery Peripartum Cardiomyopathy: An Intensivist's Perspective
Current Women`s Health Reviews Chlorophylls and their Derivatives Used in Food Industry and Medicine
Mini-Reviews in Medicinal Chemistry Development of a Sensitive Cost-Effective Capture ELISA for Detection of Murine Monoclonal Antibodies - Correlation with SPR Biosensor Technology
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Regulation of Drug Metabolism and Transporters
Current Drug Metabolism Early Intervention in Psychosis: Rationale, Results and Implications for Treatment of Adolescents at Risk
Adolescent Psychiatry EGFR High Expression, but not KRAS Status, Predicts Sensitivity of Pancreatic Cancer Cells to Nimotuzumab Treatment In Vivo
Current Cancer Drug Targets Oligodendrocyte Development and Myelination in Neurodevelopment: Molecular Mechanisms in Health and Disease
Current Pharmaceutical Design A New Role for Zn(II) Aminopeptidases: Antigenic Peptide Generation and Destruction
Current Pharmaceutical Design Editorial: Do Some Glucagon-Like-Peptide-1 Receptor Agonists (GLP-1 RA) Reduce Macrovascular Complications of Type 2 Diabetes Mellitus? (A Commentary on the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) Trial)
Current Vascular Pharmacology Immune Modulation by Plasmid DNA-mediated Cytokine Gene Transfer
Current Pharmaceutical Design CCL2 is Modulated by Cytokines and PPAR-γ in Anaplastic Thyroid Cancer
Anti-Cancer Agents in Medicinal Chemistry Assessment of Knowledge and Attitude Towards Hepatitis C Infection Among Medical and Health Science Students in Ras Al Khaimah, United Arab Emirates
Applied Clinical Research, Clinical Trials and Regulatory Affairs Nano-Curcumin Regulates p53 Phosphorylation and PAI-1 Expression during Bleomycin Induced Injury in Alveolar Basal Epithelial Cells
Current Bioactive Compounds Protein Kinase C Modulates Aurora-kinase Inhibition Induced by CCT129202 in HMC-1560,816 Cell Line
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Potential Pathogenic Inflammatory Mechanisms of Endothelial Dysfunction Induced by Type 2 Diabetes Mellitus
Current Pharmaceutical Design