Abstract
Prompted by the ineptness of the currently used non-steroidal antiinflammatory drugs (NSAIDs) to control gastric mucosal and renal adverse reactions, several ester prodrugs of ketoprofen were synthesized and characterized by IR, 1H NMR and mass spectral data. Physicochemical properties such as aqueous solubility, octanol-water partition coefficient log P, chemical stability and enzymatic hydrolysis of the synthesized molecules have been studied to assess their potential as prodrugs. The obtained results confirmed that all ester prodrugs are chemically stable, possess increased lipophilicity compared to their parent compounds and converted to the active drugs in vivo. All of the tested ester prodrugs exhibited marked anti-inflammatory activity ranging from 91.8% to 113.3% in comparison with the parent drug, ketoprofen. A mutual prodrug obtained from two antiinflammatory molecules, ketoprofen and salicylic acid has been noted to potentiate the activity making it most active molecule of the series. The ulcerogenic index of the ester prodrugs was significantly lower than the parent drug, ketoprofen. Comparative docking studies against X-ray crystal structures of COX-1 and COX-2 further provided understanding of their interaction with the cyclooxygenases that will facilitate design of better inhibitors (or prodrugs) with sufficient specificity for COX-2 against COX-1. The study offers an innovative strategy for finding a molecule with safer therapeutic profile for longterm treatment of inflammatory diseases.
Keywords: COX-1, COX-2, ester prodrugs, ketoprofen, molecular docking, NSAIDs, ulcerogenic potential.
Current Drug Discovery Technologies
Title:Ester Prodrugs of Ketoprofen: Synthesis, In Vitro Stability, In Vivo Biological Evaluation and In Silico Comparative Docking Studies Against COX-1 and COX-2
Volume: 13 Issue: 1
Author(s): Musa Ahmed, Faizul Azam, Abdul Gbaj, Abdulmottaleb E. Zetrini, Amna S. Abodlal, Abir Rghigh, Eman Elmahdi, Amel Hamza, Mabruk Salama and Salah M. Bensaber
Affiliation:
Keywords: COX-1, COX-2, ester prodrugs, ketoprofen, molecular docking, NSAIDs, ulcerogenic potential.
Abstract: Prompted by the ineptness of the currently used non-steroidal antiinflammatory drugs (NSAIDs) to control gastric mucosal and renal adverse reactions, several ester prodrugs of ketoprofen were synthesized and characterized by IR, 1H NMR and mass spectral data. Physicochemical properties such as aqueous solubility, octanol-water partition coefficient log P, chemical stability and enzymatic hydrolysis of the synthesized molecules have been studied to assess their potential as prodrugs. The obtained results confirmed that all ester prodrugs are chemically stable, possess increased lipophilicity compared to their parent compounds and converted to the active drugs in vivo. All of the tested ester prodrugs exhibited marked anti-inflammatory activity ranging from 91.8% to 113.3% in comparison with the parent drug, ketoprofen. A mutual prodrug obtained from two antiinflammatory molecules, ketoprofen and salicylic acid has been noted to potentiate the activity making it most active molecule of the series. The ulcerogenic index of the ester prodrugs was significantly lower than the parent drug, ketoprofen. Comparative docking studies against X-ray crystal structures of COX-1 and COX-2 further provided understanding of their interaction with the cyclooxygenases that will facilitate design of better inhibitors (or prodrugs) with sufficient specificity for COX-2 against COX-1. The study offers an innovative strategy for finding a molecule with safer therapeutic profile for longterm treatment of inflammatory diseases.
Export Options
About this article
Cite this article as:
Ahmed Musa, Azam Faizul, Gbaj Abdul, Zetrini E. Abdulmottaleb, Abodlal S. Amna, Rghigh Abir, Elmahdi Eman, Hamza Amel, Salama Mabruk and M. Bensaber Salah, Ester Prodrugs of Ketoprofen: Synthesis, In Vitro Stability, In Vivo Biological Evaluation and In Silico Comparative Docking Studies Against COX-1 and COX-2, Current Drug Discovery Technologies 2016; 13 (1) . https://dx.doi.org/10.2174/1570163813666160119092807
DOI https://dx.doi.org/10.2174/1570163813666160119092807 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
Related Books

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
- Announcements
Related Articles
-
Gene Therapy for Ischemic Brain Diseases
Current Gene Therapy Intracerebrally Applied Botulinum Neurotoxin in Experimental Neuroscience
Current Pharmaceutical Biotechnology The Changing Landscape of Voltage-Gated Calcium Channels in Neurovascular Disorders and in Neurodegenerative Diseases
Current Neuropharmacology Roles of TRAF6 in Central Nervous System
Current Neuropharmacology Intranasal Drug Delivery to the Central Nervous System: Present Status and Future Outlook
Current Pharmaceutical Design Macronutrient Intake and Distribution in the Etiology, Prevention and Treatment of Osteosarcopenic Obesity
Current Aging Science The Urokinase Receptor in the Central Nervous System
CNS & Neurological Disorders - Drug Targets Pharmacological Screening of Lantana camara for its Antiallergic Activity in Rodents
Clinical Anti-Inflammatory & Anti-Allergy Drugs (Discontinued) The Clinical Impact of ABCB1 Polymorphisms on the Treatment of Psychiatric Diseases
Current Pharmaceutical Design Canine Nutritional Model: Influence of Age, Diet, and Genetics on Health and Well-Being
Current Nutrition & Food Science Transitional Polytherapy: Tricks of the Trade for Monotherapy to Monotherapy AED Conversions
Current Neuropharmacology Protective Effects of Melatonin and Mitochondria-targeted Antioxidants Against Oxidative Stress: A Review
Current Medicinal Chemistry Why Anticancer Nanomedicine Needs Sugars?
Current Medicinal Chemistry Drugs Used to Treat Parkinsons Disease, Present Status and Future Directions
CNS & Neurological Disorders - Drug Targets Homocysteine and Folate Therapy in Dialysis Patients
Letters in Drug Design & Discovery Identifying Endogenous Neural Stem Cells in the Adult Brain In Vitro and In Vivo: Novel Approaches
Current Pharmaceutical Design Heavy Metal Toxicity in Humans and its Preventive and Control Measures
Current Nutrition & Food Science Therapeutic Approaches to the Challenge of Neuronal Ceroid Lipofuscinoses
Current Pharmaceutical Biotechnology Micropropagation: A Tool for the Production of High Quality Plant-based Medicines
Current Pharmaceutical Biotechnology Preface [Hot Topic: New Clinical Applications for Naturally Occurring Peptide Toxins (Guest Editors: Robert Jones / Graeme Semple)]
Current Medicinal Chemistry