Abstract
The HIV-1 integrase (IN) and reverse transcriptase (RT) are essential enzymes in the virus cycle. RT is crucial for the retrotranscription of the RNA viral genome, while IN is involved in the insertion in host chromosome of the proviral double strand DNA produced by RT. This enzyme has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. Since the discovery that catalytic cores of both HIV-1 RNase H and IN are folded in a very similar way, have very similar active site geometries, and show the same DDE triad absolutely required for catalytic activity, some researches were devoted to study IN and RNase H dual inhibitor. Our decennial interest in design and synthesis of IN inhibitors led us to study the activity of our compounds also on RNase H activity. The results of the activities showed by pyrrolyl and quinolonyl diketo acids are reported and discussed.
Keywords: HIV-1, integrase, reverse transcriptase, ribonuclease H, RNase H, RNase H inhibitor, IN inhibitor, dual inhibitors, diketo acids, pyrrole derivatives, quinolinone drivatives
Current Medicinal Chemistry
Title: Diketo Acids Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and the Reverse Transcriptase RNase H Domain
Volume: 18 Issue: 22
Author(s): R. Di Santo
Affiliation:
Keywords: HIV-1, integrase, reverse transcriptase, ribonuclease H, RNase H, RNase H inhibitor, IN inhibitor, dual inhibitors, diketo acids, pyrrole derivatives, quinolinone drivatives
Abstract: The HIV-1 integrase (IN) and reverse transcriptase (RT) are essential enzymes in the virus cycle. RT is crucial for the retrotranscription of the RNA viral genome, while IN is involved in the insertion in host chromosome of the proviral double strand DNA produced by RT. This enzyme has two associated functions: the RNA- and DNA-dependent DNA polymerase (RDDP and DDDP) and the ribonuclease H (RNase H). The RNase H function catalyzes the selective hydrolysis of the RNA strand of the RNA:DNA heteroduplex replication intermediate. Since the discovery that catalytic cores of both HIV-1 RNase H and IN are folded in a very similar way, have very similar active site geometries, and show the same DDE triad absolutely required for catalytic activity, some researches were devoted to study IN and RNase H dual inhibitor. Our decennial interest in design and synthesis of IN inhibitors led us to study the activity of our compounds also on RNase H activity. The results of the activities showed by pyrrolyl and quinolonyl diketo acids are reported and discussed.
Export Options
About this article
Cite this article as:
Di Santo R., Diketo Acids Derivatives as Dual Inhibitors of Human Immunodeficiency Virus Type 1 Integrase and the Reverse Transcriptase RNase H Domain, Current Medicinal Chemistry 2011; 18 (22) . https://dx.doi.org/10.2174/092986711796504619
DOI https://dx.doi.org/10.2174/092986711796504619 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
MicroRNAs in Human Diseases
Recent Patents on DNA & Gene Sequences Pharmacological Interventions for the Prevention and Treatment of Kidney Injury Induced by Radiotherapy: Molecular Mechanisms and Clinical Perspectives
Current Molecular Pharmacology Signal Transduction in HIV Protein-Treated Astrocytes
Current Signal Transduction Therapy HIV-1 Infected Patients have Antibodies Recognizing Folded Tat
Infectious Disorders - Drug Targets Coumarins as Inhibitors of HIV Reverse Transcriptase
Current HIV Research Novel Pentablock Copolymer Based Nanoparticles Containing Pazopanib: A Potential Therapy for Ocular Neovascularization
Recent Patents on Nanomedicine Using NMR to Develop New Allosteric and Allo-Network Drugs
Current Drug Discovery Technologies Molecular Basis for Designing Selective Modulators of Retinoic Acid Receptor Transcriptional Activities
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Triggering PIK3CA Mutations in PI3K/Akt/mTOR Axis: Exploration of Newer Inhibitors and Rational Preventive Strategies
Current Pharmaceutical Design Recent Advances in pH-Sensitive Polymeric Nanoparticles for Smart Drug Delivery in Cancer Therapy
Current Drug Targets MicroRNAs: Potential Diagnostic and Therapeutic Targets for Breast Cancer
Epigenetic Diagnosis & Therapy (Discontinued) Immunossupressant and Organ Transplantation: Immunophilins Targeting Agent and Alternative Therapies
Current Medicinal Chemistry Wrap-and-Strip Technology of Protein–Polyelectrolyte Complex for Biomedical Application
Current Medicinal Chemistry Solvent Modulation of Column Chromatography
Protein & Peptide Letters The Synthesis and Antiviral Properties of Acyclic Nucleoside Analogues with a Phosphonomethoxy Fragment in the Side Chain
Current Medicinal Chemistry Biomedical Applications of Zinc Oxide Nanomaterials
Current Molecular Medicine De Novo Malignancies After Organ Transplantation: Focus on Viral Infections
Current Molecular Medicine Epidemiology and Prevention of Viral Infections in Patients with Hematologic Malignancies
Infectious Disorders - Drug Targets The Role of Flavonoids in Inhibiting IL-6 and Inflammatory Arthritis
Current Topics in Medicinal Chemistry Effects of Highly Active Antiretroviral Therapy on HIV-1-Associated Oral Complications
Current HIV Research