Abstract
The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 IIIB. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC50 = 58.14 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.
Keywords: Drug design, guanidine indole synthesis, HIV-1 Tat, HIV-1 TAR, inhibitors.
Medicinal Chemistry
Title:Design, Synthesis and Biological Evaluation of Substituted Guanidine Indole Derivatives as Potential Inhibitors of HIV-1 Tat-TAR Interaction
Volume: 10 Issue: 7
Author(s): Jun Wang, Yan Wang, Zhenyu Li, Peng Zhan, Rujun Bai, Christophe Pannecouque, Jan Balzarini, Erik De Clercq and Xinyong Liu
Affiliation:
Keywords: Drug design, guanidine indole synthesis, HIV-1 Tat, HIV-1 TAR, inhibitors.
Abstract: The interaction between the HIV-1 transactivator protein Tat and RNA response element (TAR) plays a critical role in HIV-1 transcription. Based on the pharmacophore model of reported inhibitors, a series of novel substituted guanidine indole derivatives was designed, synthesized and evaluated for their in vitro HIV-1 and HIV-2 inhibitory activity using the IIIB strain and ROD strain, respectively. Preliminary biological evaluation indicated that three compounds exhibited marked inhibitory activity against HIV-1 IIIB. Quite unexpectedly, compound a-7 was also endowed with the moderate anti-HIV-2 potency (EC50 = 58.14 µM). In addition, preliminary discussion on the activity results and molecular modeling of these new analogues were presented in this manuscript.
Export Options
About this article
Cite this article as:
Wang Jun, Wang Yan, Li Zhenyu, Zhan Peng, Bai Rujun, Pannecouque Christophe, Balzarini Jan, Clercq De Erik and Liu Xinyong, Design, Synthesis and Biological Evaluation of Substituted Guanidine Indole Derivatives as Potential Inhibitors of HIV-1 Tat-TAR Interaction, Medicinal Chemistry 2014; 10 (7) . https://dx.doi.org/10.2174/1573406410666140306151815
DOI https://dx.doi.org/10.2174/1573406410666140306151815 |
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
-
Substance Abuse, HIV-1 and Hepatitis
Current HIV Research Theranostic Systems and Strategies for Monitoring Nanomedicine-Mediated Drug Targeting
Current Pharmaceutical Biotechnology Quantitative Structure-Activity Relationships for Anticancer Activity of 2- Phenylindoles Using Mathematical Molecular Descriptors
Current Computer-Aided Drug Design Tartrate-Resistant Acid Phosphatase: A Target for Anti-Osteoporotic Chemotherapeutics
Current Enzyme Inhibition Nutraceuticals and "Repurposed" Drugs of Phytochemical Origin in Prevention and Interception of Chronic Degenerative Diseases and Cancer
Current Medicinal Chemistry Pediatric Immune Dysfunction and Health Risks Following Early-Life Immune Insult
Current Pediatric Reviews Gene Selection in Multi-class Imbalanced Microarray Datasets Using Dynamic Length Particle Swarm Optimization
Current Bioinformatics Fibroblast Growth Factor Receptor Signaling in Cancer Biology and Treatment
Current Signal Transduction Therapy A Conceptual View on Glucocorticoid-Induced Apoptosis, Cell Cycle Arrest and Glucocorticoid Resistance in Lymphoblastic Leukemia
Current Molecular Medicine Topoisomerase I and II Inhibitors: A Patent Review
Recent Patents on Anti-Cancer Drug Discovery Implications of Somatic Mutations in the AML1/RUNX1 Gene in Myelodysplastic Syndrome (MDS): Future Molecular Therapeutic Directions for MDS
Current Cancer Drug Targets Immune Monitoring to Predict the Development of Infections After Immunosuppression for Solid Organ Transplantation and Autoimmune Diseases
Current Drug Safety New Antiangiogenetic Therapy Beyond Bevacizumab in the Treatment of Advanced Non Small Cell Lung Cancer
Current Pharmaceutical Design Practical Approach to Children Presenting with Eosinophila and Hypereosinophilia
Current Pediatric Reviews Clonetics
Current Drug Metabolism Recent Patents on Anti-Cancer Potential of Helenalin
Recent Patents on Anti-Cancer Drug Discovery Controlled-release Particulate Cytokine Adjuvants for Cancer Therapy
Endocrine, Metabolic & Immune Disorders - Drug Targets Apoptosis and Apoptosis-Based Therapy in Lung Cancer
Anti-Cancer Agents in Medicinal Chemistry Towards Improved Therapies Using Nanopharmaceuticals: Recent Patents on Pharmaceutical Nanoformulations
Recent Patents on Food, Nutrition & Agriculture Computational Modeling and Simulation of the Bcl-2 Family: Paving the Way for Rational Drug Design
Current Medicinal Chemistry