Abstract
Two series of compounds (AB and APB) bearing substituted phenoxy groups at 2-position of benzimidazole nucleus through amino or phenyleneamino were synthesized and evaluated through PASS software for predicting the activity spectrum of each compound. All compounds of both the series were predicted to have potent anthelmintic activity. The activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2 and 0.5% in terms of mortality time and paralysis time of the helminthes and was found to comply with the PASS predicted activity. In general, all compounds of APB series were more potent than those of AB series probably due to the additional hydrophobic interactions of the spacer phenyl ring in the APB series. The activity of all compounds was found to increase with increasing concentration. The compound with p-chlorophenoxy moiety was the most active from the APB series (mortality time 5.7±0.4 min and paralysis time 3.1±0.3 min) and equipotent to albendazole (mortality time 5.4±0.1 min and paralysis time 2.8±0.2 min) at concentration of 0.2%. The o-chlorophenoxy analogs in both the series were found to be the least active of all. Based on these results, a substituent capable of binding with the receptor through van der Waals and/or electronic interactions at 4-position of the phenoxy ring in the compound is suggested to increase binding interaction leading to potent anthelmintic activity.
Keywords: Benzimidazole, phenoxyacetic acid, anthelmintic, PASS, pharmacophore, intestinal worms, albendazole.
Medicinal Chemistry
Title:Design, Synthesis and PASS Assisted Evaluation of Novel 2-Substituted Benzimidazole Derivatives as Potent Anthelimintics
Volume: 10 Issue: 4
Author(s): Gurmeet Singh, Yogita Bansal, Gulshan Bansal and Rajesh Kumar Goel
Affiliation:
Keywords: Benzimidazole, phenoxyacetic acid, anthelmintic, PASS, pharmacophore, intestinal worms, albendazole.
Abstract: Two series of compounds (AB and APB) bearing substituted phenoxy groups at 2-position of benzimidazole nucleus through amino or phenyleneamino were synthesized and evaluated through PASS software for predicting the activity spectrum of each compound. All compounds of both the series were predicted to have potent anthelmintic activity. The activity of each compound was evaluated experimentally at the concentrations of 0.1, 0.2 and 0.5% in terms of mortality time and paralysis time of the helminthes and was found to comply with the PASS predicted activity. In general, all compounds of APB series were more potent than those of AB series probably due to the additional hydrophobic interactions of the spacer phenyl ring in the APB series. The activity of all compounds was found to increase with increasing concentration. The compound with p-chlorophenoxy moiety was the most active from the APB series (mortality time 5.7±0.4 min and paralysis time 3.1±0.3 min) and equipotent to albendazole (mortality time 5.4±0.1 min and paralysis time 2.8±0.2 min) at concentration of 0.2%. The o-chlorophenoxy analogs in both the series were found to be the least active of all. Based on these results, a substituent capable of binding with the receptor through van der Waals and/or electronic interactions at 4-position of the phenoxy ring in the compound is suggested to increase binding interaction leading to potent anthelmintic activity.
Export Options
About this article
Cite this article as:
Singh Gurmeet, Bansal Yogita, Bansal Gulshan and Goel Kumar Rajesh, Design, Synthesis and PASS Assisted Evaluation of Novel 2-Substituted Benzimidazole Derivatives as Potent Anthelimintics, Medicinal Chemistry 2014; 10 (4) . https://dx.doi.org/10.2174/157340641004140421115518
DOI https://dx.doi.org/10.2174/157340641004140421115518 |
Print ISSN 1573-4064 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6638 |
Call for Papers in Thematic Issues
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
-
Playing Modular Puzzle with Adhesion/Growth-Regulatory Galectins: Design and Testing of a Hybrid to Unravel Structure-Activity Relationships
Protein & Peptide Letters Recent Advances in the Membrane Receptor Initiated Vitamin D Signaling of Calcium and Phosphate Transport Across Intestinal and Kidney Epithelia
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Selection of Reprogramming Factors of Induced Pluripotent Stem Cells Based on the Protein Interaction Network and Functional Profiles
Protein & Peptide Letters Role of CCK/Gastrin Receptors in Gastrointestinal/Metabolic Diseases and Results of Human Studies Using Gastrin/CCK Receptor Agonists/Antagonists in these Diseases
Current Topics in Medicinal Chemistry Epidermolysis Bullosa: The Pediatricians Role
Current Pediatric Reviews Regulation of ABC Transporter Function Via Phosphorylation by Protein Kinases
Current Pharmaceutical Biotechnology Withdrawal Notice: Drug Repurposing for Prospective Anti-Cancer Agents Along with the Clinical Status of the Repurposed Drug
Anti-Cancer Agents in Medicinal Chemistry Trifluoroibuprofen Inhibits α-Methylacyl Coenzyme A Racemase (AMACR/P504S), Reduces Cancer Cell Proliferation and Inhibits in vivo Tumor Growth in Aggressive Prostate Cancer Models
Anti-Cancer Agents in Medicinal Chemistry ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases
Current Pharmaceutical Design Histone Deacetylase Inhibition: A Differentiation Therapy for Cultured Primary Hepatocytes?
Current Enzyme Inhibition Discovery of New Biomarkers of Cancer Using Proteomics Technology
Current Cancer Therapy Reviews Mechanism of Action of Flavonoids in Prevention of Inflammation- Associated Skin Cancer
Current Medicinal Chemistry The ATP-driven Hsp60 Machinery: Biological and Clinical Implications
Current Immunology Reviews (Discontinued) Targeting the Hedgehog Pathway for Locally Advanced and Metastatic Basal Cell Carcinoma
Current Pharmaceutical Design The Role of dUTPase and Uracil-DNA Repair in Cancer Chemotherapy
Current Protein & Peptide Science Nanotechology-Based Strategies to Enhance the Efficacy of Photodynamic Therapy for Cancers
Current Drug Metabolism MicroRNA: Implications for Alzheimer Disease and other Human CNS Disorders
Current Genomics Resveratrol in Medicinal Chemistry: A Critical Review of its Pharmacokinetics, Drug-Delivery, and Membrane Interactions
Current Medicinal Chemistry Role of Genomic Alterations in HER2 Positive Breast Carcinoma: Focus on Susceptibility and Trastuzumab-therapy
Current Cancer Drug Targets Regenerative Medicine: Does Erythropoietin have a Role?
Current Pharmaceutical Design