Abstract
HIV cellular entry is a multistep process that requires the interaction of a viral envelope glycoprotein (gp120) and a host receptor (CD4) followed by binding to a co-receptor. The CC-chemokine receptor 5 (CCR5) and CXC-chemokine receptor 4 (CXCR4) have been identified as the major HIV co-receptors and therefore are promising targets for the development of new anti-HIV drugs. CXCR4 is also involved in several diseases such as angiogenesis, metabolic and neurological disorders, rheumatoid arthritis and in different forms of metastatic cancer. Herein, we present a review focusing on small molecule CXCR4 antagonists. These compounds are divided into 11 classes that include cyclic penta- and tetrapeptides, diketopiperazine mimetics, bicyclams, non-bicyclams, tetrahydroquinolines, thiazolylisothiourea derivatives, benzodiazepines, alkyl amine analogs and non-peptides derivatives, dipicolylamine-zinc(II) complexes, ampelopsin and distamycin analogs. The most advanced CXCR4 antagonists documented are bicyclam derivatives, which are specific CXCR4 antagonists and exhibit potency in the nanomolar range. Further development of selective CXCR4 antagonists continues to be crucial for the design of second generation of anti-HIV drugs. We aim to provide a comprehensive summary of diverse structural templates that could be useful for optimization and discovery of novel CXCR4 antagonists.
Keywords: HIV infection, chemokine receptors, CXCR4 antagonists
Current Pharmaceutical Design
Title: Small Molecules Anti-HIV Therapeutics Targeting CXCR4
Volume: 14 Issue: 4
Author(s): Nouri Neamati, Fedora Grande and Antonio Garofalo
Affiliation:
Keywords: HIV infection, chemokine receptors, CXCR4 antagonists
Abstract: HIV cellular entry is a multistep process that requires the interaction of a viral envelope glycoprotein (gp120) and a host receptor (CD4) followed by binding to a co-receptor. The CC-chemokine receptor 5 (CCR5) and CXC-chemokine receptor 4 (CXCR4) have been identified as the major HIV co-receptors and therefore are promising targets for the development of new anti-HIV drugs. CXCR4 is also involved in several diseases such as angiogenesis, metabolic and neurological disorders, rheumatoid arthritis and in different forms of metastatic cancer. Herein, we present a review focusing on small molecule CXCR4 antagonists. These compounds are divided into 11 classes that include cyclic penta- and tetrapeptides, diketopiperazine mimetics, bicyclams, non-bicyclams, tetrahydroquinolines, thiazolylisothiourea derivatives, benzodiazepines, alkyl amine analogs and non-peptides derivatives, dipicolylamine-zinc(II) complexes, ampelopsin and distamycin analogs. The most advanced CXCR4 antagonists documented are bicyclam derivatives, which are specific CXCR4 antagonists and exhibit potency in the nanomolar range. Further development of selective CXCR4 antagonists continues to be crucial for the design of second generation of anti-HIV drugs. We aim to provide a comprehensive summary of diverse structural templates that could be useful for optimization and discovery of novel CXCR4 antagonists.
Export Options
About this article
Cite this article as:
Neamati Nouri, Grande Fedora and Garofalo Antonio, Small Molecules Anti-HIV Therapeutics Targeting CXCR4, Current Pharmaceutical Design 2008; 14 (4) . https://dx.doi.org/10.2174/138161208783497714
DOI https://dx.doi.org/10.2174/138161208783497714 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Angiogenesis New Targets for the Development of Anticancer Chemotherapies
Current Pharmaceutical Design Frailty of Older Age: The Role of the Endocrine - Immune Interaction
Current Pharmaceutical Design Insights on Biology and Pathology of HIF-1α/-2α, TGFβ/BMP, Wnt/β-Catenin, and NF-κB Pathways in Osteoarthritis
Current Pharmaceutical Design Anti-Tumor Monoclonal Antibodies in Conjunction with β-Glucans: A Novel Anti- Cancer Immunotherapy
Current Medicinal Chemistry Oxidative Stress on Progenitor and Stem Cells in Cardiovascular Diseases
Current Pharmaceutical Biotechnology Determination of Body Mass Index and Physical Activity in Normal Weight Children and Evaluation of Salivary Levels of Interleukin 10 and Interleukin 17
Clinical Immunology, Endocrine & Metabolic Drugs (Discontinued) The Use of Statins in Respiratory Diseases
Current Respiratory Medicine Reviews Antimalarial Drugs and their Useful Therapeutic Lives: Rational Drug Design Lessons from Pleiotropic Action of Quinolines and Artemisinins
Current Drug Discovery Technologies Unusual Cerebral Involvement of Rheumatoid Arthritis Mimicking a Tumor
Current Medical Imaging The Haywain: Anti-synthetase Antibodies in Patients with Inflammatory Diseases: Targeting Monocytes or Neutrophils?
Current Medicinal Chemistry Antipsoriatic Drug Development: Challenges and New Emerging Therapies
Recent Patents on Inflammation & Allergy Drug Discovery Interleukin-21 in Immune and Allergic Diseases
Inflammation & Allergy - Drug Targets (Discontinued) The Gut Microbiota and the Emergence of Autoimmunity: Relevance to Major Psychiatric Disorders
Current Pharmaceutical Design Effects of Plants and Isolates of Celastraceae Family on Cancer Pathways
Anti-Cancer Agents in Medicinal Chemistry pNitro-Tyr-PseAAC: Predict Nitrotyrosine Sites in Proteins by Incorporating Five Features into Chou’s General PseAAC
Current Pharmaceutical Design SERMs: Evolutionary Chemistry, Revolutionary Biology
Current Pharmaceutical Design Glucocorticoids in Patients with Rheumatic Diseases: Friends or Enemies of Bone?
Current Medicinal Chemistry Immunomodulatory Activity of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Kruppel-Like Factor 2 (KLF2) Regulates Monocyte Differentiation and Functions in mBSA and IL-1β-Induced Arthritis
Current Molecular Medicine Inflammation: A Link Between Hypertension and Atherosclerosis
Current Hypertension Reviews