Abstract
Tuberculosis infections of the central nervous system are a serious and often fatal disease predominantly impacting young children. Having a success rate of approximately 10%, an in silico data mining search generated 23 analogs to isoniazid, which is a first-line tuberculostatic. All analogs retained the hydrazide functional group in addition to configurations including: quinoline, pyridine, indole, quinolin-4-ol, quinoline-2,4-diol, and pyridine-2-one. Studies have shown that brain penetration is optimal when polar surface area is less than 90 A2. Sixteen of generated analogs have polar surface area less than 70 A2 (drugs 1, 2, 3, 4, 5, 6, 8, 11, 13, 14, 15, 16, 18, 19, 22, and 23) and six analogs have values between 70 A2 to 90 A2 (drugs 7, 9, 10, 12, 17, 21). All agents showed zero violations of the Rule of 5 which indicates favorable druglikeness. The aqueous solubility, formula weight, molecular volume, polar surface area, and Log P properties are determined. Pattern recognition analysis such as hierarchical cluster analysis, discriminate analysis, and ANOSIM identified underlying relationships among these 24 drugs that is based upon important pharmaceutical properties. Global resurgence of tuberculosis and the rapid emergence of multidrug resistant tuberculosis underscore the importance of the development of new tuberculostatic drugs.
Keywords: Tuberculostatic, mycobacterium tuberculosis, isoniazid, tuberculosis
Anti-Infective Agents
Title:Tuberculostatic Drugs Targeting Infections of the Central Nervous System
Volume: 10 Issue: 2
Author(s): Ronald Bartzatt
Affiliation:
Keywords: Tuberculostatic, mycobacterium tuberculosis, isoniazid, tuberculosis
Abstract: Tuberculosis infections of the central nervous system are a serious and often fatal disease predominantly impacting young children. Having a success rate of approximately 10%, an in silico data mining search generated 23 analogs to isoniazid, which is a first-line tuberculostatic. All analogs retained the hydrazide functional group in addition to configurations including: quinoline, pyridine, indole, quinolin-4-ol, quinoline-2,4-diol, and pyridine-2-one. Studies have shown that brain penetration is optimal when polar surface area is less than 90 A2. Sixteen of generated analogs have polar surface area less than 70 A2 (drugs 1, 2, 3, 4, 5, 6, 8, 11, 13, 14, 15, 16, 18, 19, 22, and 23) and six analogs have values between 70 A2 to 90 A2 (drugs 7, 9, 10, 12, 17, 21). All agents showed zero violations of the Rule of 5 which indicates favorable druglikeness. The aqueous solubility, formula weight, molecular volume, polar surface area, and Log P properties are determined. Pattern recognition analysis such as hierarchical cluster analysis, discriminate analysis, and ANOSIM identified underlying relationships among these 24 drugs that is based upon important pharmaceutical properties. Global resurgence of tuberculosis and the rapid emergence of multidrug resistant tuberculosis underscore the importance of the development of new tuberculostatic drugs.
Export Options
About this article
Cite this article as:
Bartzatt Ronald, Tuberculostatic Drugs Targeting Infections of the Central Nervous System, Anti-Infective Agents 2012; 10 (2) . https://dx.doi.org/10.2174/2211362611208020087
DOI https://dx.doi.org/10.2174/2211362611208020087 |
Print ISSN 2211-3525 |
Publisher Name Bentham Science Publisher |
Online ISSN 2211-3533 |
Call for Papers in Thematic Issues
An Overview of Drugs for Multiple Targets and Variants of SARS-CoV-2 Through Artificial Intelligence, Machine Learning, Deep Learning, and Experimental Analysis
The emergence and rapid evolution of SARS-CoV-2 variants have posed significant challenges in the ongoing fight against the COVID-19 pandemic. The development of effective treatments for multiple viral targets and variants demands innovative approaches, including artificial intelligence (AI), machine learning (ML), and deep learning (DL) techniques. This special issue aims ...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
-
Compendious Review on Bioactive Constituents and Pharmacotherapeutic
Profile of Heliotropium indicum Linn
The Natural Products Journal Natural Products as Leads for Tuberculosis Drug Development
Current Topics in Medicinal Chemistry Ureas: Applications in Drug Design
Current Medicinal Chemistry Desferrioxamine as Immunomodulatory Agent During Microorganism Infection
Current Pharmaceutical Design Drugs that Inhibit Mycolic Acid Biosynthesis in Mycobacterium tuberculosis
Current Pharmaceutical Biotechnology Novel Pharmacologic Approaches to the Management of Sepsis: Targeting the Host Inflammatory Response
Recent Patents on Inflammation & Allergy Drug Discovery Nano-carriers for the Treatment of Tuberculosis
Recent Patents on Anti-Infective Drug Discovery Atranorin – An Interesting Lichen Secondary Metabolite
Mini-Reviews in Medicinal Chemistry Rheumatic Manifestations in Malignancy
Current Rheumatology Reviews Immune Monitoring to Predict the Development of Infections After Immunosuppression for Solid Organ Transplantation and Autoimmune Diseases
Current Drug Safety Influence of Leptin on Immunity
Current Immunology Reviews (Discontinued) Chemotherapeutic Strategies Against Trypanosoma brucei: Drug Targets vs. Drug Targeting
Current Pharmaceutical Design Pharmacogenetic Polymorphisms in a Portuguese Gypsy Population
Current Pharmacogenomics and Personalized Medicine Synthetic Polyacrylate Polymers as Particulate Intranasal Vaccine Delivery Systems for the Induction of Mucosal Immune Response
Current Drug Delivery Therapeutic Implications of Tocilizumab, A Humanized Anti-Interleukin-6 Receptor Antibody, for Various Immune-Mediated Diseases: An Update Review
Current Rheumatology Reviews Serum and Bronchoalveolar Lavage Fluid 25(OH)Vitamin D3 Levels in HIV-1 and Tuberculosis: A Cross-Sectional Study from a Tertiary Care Center in North India
Current HIV Research Meet Our Editorial Board Member
The Natural Products Journal p53-Induced Apoptosis and Inhibitors of p53
Current Medicinal Chemistry Ototoxicity: Mechanisms of Cochlear Impairment and its Prevention
Current Medicinal Chemistry Balancing the Double-Edged Sword: Metal Ion Homeostasis and the Ulcer Bug
Current Medicinal Chemistry