Abstract
A few celecosib like 1,5-diarylpyrazoles conjugated with nitric oxide (NO) donating nitrate ester group were synthesized and evaluated for their selective COX-2 inhibitory activity along with NO releasing ability of corresponding nitrate esters. Most of the synthesized compounds exhibited improved COX-2 inhibition when compared with the reference drug celecoxib. The nitrate ester derivatives (coxib prodrugs) 7 (nitrate ester of 1,5-diarylpyrazole with 2 carbon linker), and 9 (nitrate ester of 1,5-diarylpyrazole with 3 carbon linker), upon incubation in human whole blood were partly transformed into the corresponding alcohols 6, and 8 respectively. Molecular docking studies were performed on alcohol derivatives and revealed additional H-bond interactions compared to celecoxib.
Keywords: CINODs, COX-2 inhibition, Coxib prodrugs, 1, 5-Diarylpyrazoles, Nitrate esters, NO-Donors.
Letters in Drug Design & Discovery
Title:Synthesis of 1,5-Diarylpyrazoles as Potential COX-2 Inhibitors with Nitric Oxide Releasing Ability
Volume: 10 Issue: 7
Author(s): Bolla Narasimha Rao, Meyyappan Muthuppalaniappan, Saketh Sriram Dinavahi, Srikant Viswanadha, Chandrakant Bagul, Kolupula Srinivas, Swaroop Kumar V. S. Vakkalanka, Krishnam Raju Atcha and Ahmed Kamal
Affiliation:
Keywords: CINODs, COX-2 inhibition, Coxib prodrugs, 1, 5-Diarylpyrazoles, Nitrate esters, NO-Donors.
Abstract: A few celecosib like 1,5-diarylpyrazoles conjugated with nitric oxide (NO) donating nitrate ester group were synthesized and evaluated for their selective COX-2 inhibitory activity along with NO releasing ability of corresponding nitrate esters. Most of the synthesized compounds exhibited improved COX-2 inhibition when compared with the reference drug celecoxib. The nitrate ester derivatives (coxib prodrugs) 7 (nitrate ester of 1,5-diarylpyrazole with 2 carbon linker), and 9 (nitrate ester of 1,5-diarylpyrazole with 3 carbon linker), upon incubation in human whole blood were partly transformed into the corresponding alcohols 6, and 8 respectively. Molecular docking studies were performed on alcohol derivatives and revealed additional H-bond interactions compared to celecoxib.
Export Options
About this article
Cite this article as:
Rao Narasimha Bolla, Muthuppalaniappan Meyyappan, Dinavahi Sriram Saketh, Viswanadha Srikant, Bagul Chandrakant, Srinivas Kolupula, Vakkalanka Kumar V. S. Swaroop, Atcha Raju Krishnam and Kamal Ahmed, Synthesis of 1,5-Diarylpyrazoles as Potential COX-2 Inhibitors with Nitric Oxide Releasing Ability, Letters in Drug Design & Discovery 2013; 10 (7) . https://dx.doi.org/10.2174/1570180811310070006
DOI https://dx.doi.org/10.2174/1570180811310070006 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
- 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
-
Peroxynitrite-Mediated Structural Changes in Histone H2A: Biochemical and Biophysical Analysis
Protein & Peptide Letters Hybrid-Based Multi-Target Ligands for the Treatment of Alzheimer's Disease
Current Topics in Medicinal Chemistry Combretastatin A-4 Analogs as Anticancer Agents
Mini-Reviews in Medicinal Chemistry 1,2,4-Triazine Analogs as Novel Class of Therapeutic Agents
Mini-Reviews in Medicinal Chemistry Peptides Targeting Gap Junctional Structures
Current Pharmaceutical Design Dipeptidyl-peptidase 4 Inhibition: Linking Metabolic Control to Cardiovascular Protection
Current Pharmaceutical Design Using Pharmacogenomic Tumor Profiling to Identify Biomarkers of 5-fluorouracil Response in Colorectal Cancer
Current Pharmacogenomics Bioprecursor Prodrugs: Molecular Modification of the Active Principle
Mini-Reviews in Medicinal Chemistry Thalidomide in Multiple Myeloma
Current Pharmaceutical Biotechnology Lysine-derived Alkaloids: Overview and Update on Biosynthesis and Medicinal Applications with Emphasis on Quinolizidine Alkaloids
Mini-Reviews in Medicinal Chemistry Gene Expression Studies to Investigate Disease Mechanisms in Rheumatoid Arthritis: Does Angiogenesis Play a Role?
Current Rheumatology Reviews Dietary Lutein and Zeaxanthin in the Prevention of Age-Related Macular Degeneration in the Elderly
Current Nutrition & Food Science Pleiotropic Effects of Cardioactive Glycosides
Current Medicinal Chemistry What Have We Learned from the Novel Human Cytochromes P450 Hidden in the Databases?
Current Genomics Programmed Cell Death after Intracerebral Hemorrhage
Current Neuropharmacology Experimental Fracture Protocols in Assessments of Potential Agents for Osteoporotic Fracture Healing Using Rodent Models
Current Drug Targets The φC31 Integrase System for Gene Therapy
Current Gene Therapy The Assessment and Characterisation of Drug Plasma Protein Binding in the Body Using QSAR
Mini-Reviews in Medicinal Chemistry Retracted: Tocotrienols and its Role in Cardiovascular Health- a Lead for Drug Design
Current Pharmaceutical Design Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Endocrine, Metabolic & Immune Disorders - Drug Targets