Abstract
Background: Immunosuppressive drugs are widely used to prevent and treat allograft rejection and autoimmune diseases. Mycophenolic acid (MPA) and its derivatives are currently one of the most prescribed immunosuppressive drugs; however, metabolic drawbacks and variable interand intrapatient responses limit their use.
Objective: In order to find out new safe and effective immunosuppressive compounds, we report here the synthesis and pharmacological evaluation of hybrid MPA derivatives containing the thalidomide/ phthalimide subunits. Results: All compounds 3a-d exhibited an enhanced ability to reduce the levels of pro-inflammatory cytokines compared to the parental drugs MPA and thalidomide. The mixed lymphocyte reaction assay has demonstrated that compound 3d - (E)-(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1- yl)methyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enoate – has superior activity compared to that of MPA. In addition, compound 3d was less cytotoxic against Jurkat cells than MPA and did not demonstrate in vivo genotoxic effect. Conclusion: All these data have shown that compound 3d is a promising lead compound useful in the immunosuppressive therapy.Keywords: Immunossupression, mycophenolic acid, thalidomide, mixed lymphocyte reaction assay, immunossupressive drugs.
Medicinal Chemistry
Title:Synthesis and Immunosuppressive Activity of New Mycophenolic Acid Derivatives
Volume: 13 Issue: 2
Author(s): Karina P. Barbieri, Lucas dos R. Ercolin, Thierry Louat, Marisa C. Polesi, Chung M. Chin, Iracilda C. Zeppone and Jean L. dos Santos
Affiliation:
Keywords: Immunossupression, mycophenolic acid, thalidomide, mixed lymphocyte reaction assay, immunossupressive drugs.
Abstract: Background: Immunosuppressive drugs are widely used to prevent and treat allograft rejection and autoimmune diseases. Mycophenolic acid (MPA) and its derivatives are currently one of the most prescribed immunosuppressive drugs; however, metabolic drawbacks and variable interand intrapatient responses limit their use.
Objective: In order to find out new safe and effective immunosuppressive compounds, we report here the synthesis and pharmacological evaluation of hybrid MPA derivatives containing the thalidomide/ phthalimide subunits. Results: All compounds 3a-d exhibited an enhanced ability to reduce the levels of pro-inflammatory cytokines compared to the parental drugs MPA and thalidomide. The mixed lymphocyte reaction assay has demonstrated that compound 3d - (E)-(3-(1,3-dioxoisoindolin-2-yl)-2,6-dioxopiperidin-1- yl)methyl-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1,3-dihydroisobenzofuran-5-yl)-4-methylhex-4- enoate – has superior activity compared to that of MPA. In addition, compound 3d was less cytotoxic against Jurkat cells than MPA and did not demonstrate in vivo genotoxic effect. Conclusion: All these data have shown that compound 3d is a promising lead compound useful in the immunosuppressive therapy.Export Options
About this article
Cite this article as:
Barbieri P. Karina, Ercolin dos R. Lucas, Louat Thierry, Polesi C. Marisa, Chin M. Chung, Zeppone C. Iracilda and Santos L. dos Jean, Synthesis and Immunosuppressive Activity of New Mycophenolic Acid Derivatives, Medicinal Chemistry 2017; 13 (2) . https://dx.doi.org/10.2174/1573406412666161207121226
DOI https://dx.doi.org/10.2174/1573406412666161207121226 |
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
-
NF-κB Inhibitors for the Treatment of Inflammatory Diseases and Cancer
Current Medicinal Chemistry Emerging Indications for Statins: A Pluripotent Family of Agents with Several Potential Applications
Current Pharmaceutical Design Systemic Immunomodulation of Autoimmune Disease Using MHC-Derived Recombinant TCR Ligands
Current Drug Targets - Inflammation & Allergy Current Status of Vitamin D Signaling and Its Therapeutic Applications
Current Topics in Medicinal Chemistry From Cannabis to Endocannabinoids in Multiple Sclerosis: A Paradigm of Central Nervous System Autoimmune Diseases
Current Drug Targets - CNS & Neurological Disorders Radiolabelled Quinoline Derivaties for the PET Imaging of Peripheral Benzodiazepine Receptor
Current Medical Imaging Serological Electrodetection of Rheumatoid Arthritis Using Mimetic Peptide
Protein & Peptide Letters Micronutrients at the Interface Between Inflammation and Infection Ascorbic Acid and Calciferol. Part 2: Calciferol and the Significance of Nutrient Supplements
Inflammation & Allergy - Drug Targets (Discontinued) Current Immune Therapies of Autoimmune Disease of the Nervous System with Special Emphasis to Multiple Sclerosis
Current Pharmaceutical Design Novel Carriers for Coenzyme Q10 Delivery
Current Drug Delivery Update on Pathogenesis of Sjogren's Syndrome
Current Rheumatology Reviews S1P Receptor Modulators in Cell Trafficking and Therapeutics
Current Immunology Reviews (Discontinued) Control of Interleukin-1β Secretion in Inflammation and Immune Response
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Therapeutic Antibodies in HIV Treatment - Classical Approaches to Novel Advances
Current Pharmaceutical Design The Role of Anaphylatoxins C3a and C5a in Regulating Innate and Adaptive Immune Responses
Inflammation & Allergy - Drug Targets (Discontinued) The Expanding Role of APRIL in Cancer and Immunity
Current Molecular Medicine Treatment of Central Nervous System Involvement Associated with Primary Sjogrens Syndrome
Current Pharmaceutical Design Recent Trials for FTY720 (Fingolimod): A New Generation of Immunomodulators Structurally Similar to Sphingosine
Reviews on Recent Clinical Trials Recent Patents Concerning Modulators of Protein Kinase C
Recent Patents on DNA & Gene Sequences Negative Regulation of TCR Signaling in Immunological Tolerance: Taming Good and Evil
Current Immunology Reviews (Discontinued)