Abstract
A series of novel ethyl 1-(2-(4-(2-amino-5-(ethoxycarbonyl) phenyl) piperazin-1-yl) ethyl)-2-(2-(substituted) pyridin-3-yl)-1H-benzo[d]imidazole-5-carboxylate analogues were synthesized and screened as p38 MAP kinase inhibitors. The 4-chlorophenoxy substitution in the 2nd position of the pyridyl moiety (5i) gave effective inhibition of p38 with IC50 17µM. Moreover, the synthesized benzimidazole derivatives possess a significant antiproliferative activity against blood-leukemia (CCRF-CEM), colon (HCT-116) and breast (MDA-MB-468) cancer cell lines. Based on the report, we discussed structure-activity relationship (SAR) study of synthesized benzimidazole derivatives. Molecular modelling performed for the identification of most active compounds by using three dimensional crystal structures of MAPK p38, provide a disclosed binding template of these inhibitors in the active site of their respective enzyme.
Keywords: Benzimidazole, pyridine, MAPK p38, leukemia, colon cancer, breast cancer.
Letters in Drug Design & Discovery
Title:Synthesis and Evaluation of Compounds Containing 4-arylpiperazinyl Moieties Linked to a 2-(pyridin-3-yl)-1H-benzimidazole as p38 MAP Kinase Inhibitors
Volume: 13 Issue: 7
Author(s): Mohamed Ashraf Ali, Hasnah Osman, Raju Suresh Kumar, Abdulrahman I. Almansour, Natarajan Arumugam, Vijay H. Masand and Theivendren Panneerselvam
Affiliation:
Keywords: Benzimidazole, pyridine, MAPK p38, leukemia, colon cancer, breast cancer.
Abstract: A series of novel ethyl 1-(2-(4-(2-amino-5-(ethoxycarbonyl) phenyl) piperazin-1-yl) ethyl)-2-(2-(substituted) pyridin-3-yl)-1H-benzo[d]imidazole-5-carboxylate analogues were synthesized and screened as p38 MAP kinase inhibitors. The 4-chlorophenoxy substitution in the 2nd position of the pyridyl moiety (5i) gave effective inhibition of p38 with IC50 17µM. Moreover, the synthesized benzimidazole derivatives possess a significant antiproliferative activity against blood-leukemia (CCRF-CEM), colon (HCT-116) and breast (MDA-MB-468) cancer cell lines. Based on the report, we discussed structure-activity relationship (SAR) study of synthesized benzimidazole derivatives. Molecular modelling performed for the identification of most active compounds by using three dimensional crystal structures of MAPK p38, provide a disclosed binding template of these inhibitors in the active site of their respective enzyme.
Export Options
About this article
Cite this article as:
Ali Ashraf Mohamed, Osman Hasnah, Kumar Suresh Raju, I. Almansour Abdulrahman, Arumugam Natarajan, H. Masand Vijay and Panneerselvam Theivendren, Synthesis and Evaluation of Compounds Containing 4-arylpiperazinyl Moieties Linked to a 2-(pyridin-3-yl)-1H-benzimidazole as p38 MAP Kinase Inhibitors, Letters in Drug Design & Discovery 2016; 13 (7) . https://dx.doi.org/10.2174/1570180812666151022221401
DOI https://dx.doi.org/10.2174/1570180812666151022221401 |
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
-
Effects of Hypertension, Diabetes Mellitus, Obesity and Other Factors on Kidney Haemodynamics
Current Vascular Pharmacology New Lipid Modulating Drugs: The Role of Microsomal Transport Protein Inhibitors
Current Pharmaceutical Design The Role of Nitric Oxide on Endothelial Function
Current Vascular Pharmacology The role of interleukin 35 in atherosclerosis
Current Pharmaceutical Design The Metabolism of Anthocyanins
Current Drug Metabolism Evaluating 3D-printed Bolus Compared to Conventional Bolus Types Used in External Beam Radiation Therapy
Current Medical Imaging Catechol-O-Methyltransferase (COMT)-Mediated Methylation Metabolism of Endogenous Bioactive Catechols and Modulation by Endobiotics and Xenobiotics: Importance in Pathophysiology and Pathogenesis
Current Drug Metabolism Meet Our Editorial Board Member
Current Drug Delivery Effect of Fasting Ramadan in Diabetes Control Status - Application of Extensive Diabetes Education, Serum Creatinine with HbA1c Statistical ANOVA and Regression Models to Prevent Hypoglycemia
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Determination of Homocysteine in Human Saliva by Liquid Chromatography and Electrospray Ionization Quadrupole Time-of-flight Mass Spectrometry: Profiles in Healthy Adults
Protein & Peptide Letters Protein-protein Interactions: Network Analysis and Applications in Drug Discovery
Current Pharmaceutical Design An Update on the Role of the Quality of LDL in Cardiovascular Risk:The Contribution of the Universities of Palermo and Zurich
Recent Patents on Cardiovascular Drug Discovery Biomarkers of Oxidative Stress and the Relationship to Cigarette Smoking
Mini-Reviews in Organic Chemistry Subject Index To Volume 12
Current Pharmaceutical Design Psychotropics and Methadone in Acquired Long QT Syndrome
Current Psychopharmacology The Polymorphism at the microRNA-155 Binding Site in the AGTR1 Gene is not Significantly Associated with Rheumatic Heart Disease in Saudi Arabia Population
MicroRNA An Update on the Cardiovascular Effects of Quercetin, a Plant Flavonoid
Current Nutrition & Food Science The Neuroprotective Effect of Ginkgo biloba Leaf Extract and its Possible Mechanism
Central Nervous System Agents in Medicinal Chemistry Hypocholesterolemia
Current Vascular Pharmacology Polyphenols can Potentially Prevent Atherosclerosis and Cardiovascular Disease by Modulating Macrophage Cholesterol Metabolism
Current Molecular Pharmacology