Abstract
Background: Despite of the globally positive trends in the epidemiology of tuberculosis, the increasing rates of drug-resistant strains are urging to introduce new antituberculars into clinical practice. Development of a new chemical entity from hit to marketed drug is an extremely time and resources consuming process with uncertain outcome. Repurposing of clinically used drugs can be a cheaper alternative to develop new drugs effective in the treatment of tuberculosis.
Objective: To extract the latest information on new mechanisms of action described or proposed for clinically used antitubercular drugs. To identify drugs from various pharmacodynamic groups as candidates for repurposing to become effective in combatting tuberculosis. Attention will be paid to elucidate the connection between repurposed drugs and new antituberculars in clinical practice or in clinical trials.
Methods: Scientific databases were searched for the keywords.
Results: We reviewed the latest aspects of usage and new mechanisms of action for both first-line and second-line antitubercular drugs in clinical practice. Further, we found that surprisingly large number of clinically used drugs from various pharmacodynamic groups have potential to be used in the treatment of tuberculosis, including antimicrobial drugs not typically used against tuberculosis, statins, CNS drugs (tricyclic phenothiazines, antidepressants, anticonvulsants), non-steroidal anti-inflammatory drugs, kinase inhibitors, and others (metformin, disulfiram, verapamil, lansoprazole). Repurposed drugs may become effective antituberculars, acting either by direct effects on mycobacteria or as adjunct, host-directed therapy.
Conclusion: In this review, we showed that proper research of old drugs is a very efficient tool to develop new antituberculars.
Keywords: Antitubercular, mechanism of action, tuberculosis, repurposed drugs, repositioned drugs, promiscuous drugs, multitarget drugs.
Current Medicinal Chemistry
Title:Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis
Volume: 25 Issue: 38
Author(s): Jan Zitko*Martin Doležal
Affiliation:
- Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove,Czech Republic
Keywords: Antitubercular, mechanism of action, tuberculosis, repurposed drugs, repositioned drugs, promiscuous drugs, multitarget drugs.
Abstract: Background: Despite of the globally positive trends in the epidemiology of tuberculosis, the increasing rates of drug-resistant strains are urging to introduce new antituberculars into clinical practice. Development of a new chemical entity from hit to marketed drug is an extremely time and resources consuming process with uncertain outcome. Repurposing of clinically used drugs can be a cheaper alternative to develop new drugs effective in the treatment of tuberculosis.
Objective: To extract the latest information on new mechanisms of action described or proposed for clinically used antitubercular drugs. To identify drugs from various pharmacodynamic groups as candidates for repurposing to become effective in combatting tuberculosis. Attention will be paid to elucidate the connection between repurposed drugs and new antituberculars in clinical practice or in clinical trials.
Methods: Scientific databases were searched for the keywords.
Results: We reviewed the latest aspects of usage and new mechanisms of action for both first-line and second-line antitubercular drugs in clinical practice. Further, we found that surprisingly large number of clinically used drugs from various pharmacodynamic groups have potential to be used in the treatment of tuberculosis, including antimicrobial drugs not typically used against tuberculosis, statins, CNS drugs (tricyclic phenothiazines, antidepressants, anticonvulsants), non-steroidal anti-inflammatory drugs, kinase inhibitors, and others (metformin, disulfiram, verapamil, lansoprazole). Repurposed drugs may become effective antituberculars, acting either by direct effects on mycobacteria or as adjunct, host-directed therapy.
Conclusion: In this review, we showed that proper research of old drugs is a very efficient tool to develop new antituberculars.
Export Options
About this article
Cite this article as:
Zitko Jan*, Doležal Martin , Old Drugs and New Targets as an Outlook for the Treatment of Tuberculosis, Current Medicinal Chemistry 2018; 25 (38) . https://dx.doi.org/10.2174/0929867324666170920154325
DOI https://dx.doi.org/10.2174/0929867324666170920154325 |
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
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...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
- 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
-
Recent Advances in Understanding and Management of Chronic Granulomatous Disease
Current Immunology Reviews (Discontinued) Synthesis and <i>In-silico</i> Identification of New Bioactive 1,3,4-oxadiazole Tagged 2,3-dihydroimidazo[1,2-a]pyridine Derivatives
Current Bioactive Compounds ent-Abietane Lactones from Euphorbia
Mini-Reviews in Medicinal Chemistry Antitubercular and Antimicrobial Activity of NH4VO3 Promoted 1,4- Dihydropyridine Incorporated 1,3,4-trisubstituted Pyrazole
Letters in Drug Design & Discovery A Novel Feature-Significance Based k-Nearest Neighbour Classification Approach for Computer Aided Diagnosis of Lung Disorders
Current Medical Imaging Asthma in Childhood – Making the Diagnosis
Current Pediatric Reviews Lipids as Biomarkers of Cancer and Bacterial Infections
Current Medicinal Chemistry Editorial (Thematic Issue: The Lab-on-a-protein Concept Protein as Powerful Nanometric Laboratory for Chemical Sciences)
Current Organic Chemistry Trends and Economic Stress: A Challenge to Universal Access to Antiretroviral Treatment in India
Current HIV Research Coumarine Analogues with Antimycobacterial and Immunomodulatory Activity
Current Bioactive Compounds New Adamantyl Chalcones: Synthesis, Antimicrobial and Anticancer Activities
Current Topics in Medicinal Chemistry Crystallization of Cytochromes P450 and Substrate-Enzyme Interactions
Current Topics in Medicinal Chemistry Dietary Antioxidants: Immunity and Host Defense
Current Topics in Medicinal Chemistry A Pharmacological Review of Five Widely Used Traditional Medicinal Plants for Sedative-Hypnotic Effects in Bangladesh
Current Traditional Medicine New Insights into Lipidic Secondary Metabolites in Mycobacteria
Current Chemical Biology miR-15b and miR-21 as Circulating Biomarkers for Diagnosis of Glioma
Current Genomics A Case of Neurosarcoidosis Mimicking Brain Tumor
Current Medical Imaging Association of Serum Malondialdehyde and C-reactive Protein Levels with Exacerbations of Chronic Obstructive Pulmonary Disease
Current Respiratory Medicine Reviews A Review: G-Quadruplex’s Applications in Biological Target Detection and Drug Delivery
Current Topics in Medicinal Chemistry In Silico Screening for Potent Inhibitors against the NS3/4A Protease of Hepatitis C Virus
Current Pharmaceutical Design