Abstract
Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest.
Keywords: Macrolide Hybrid, Azalide, Antibacterial, Antimalarial, Anti-inflammatory, Quinolone, Quinoline, Corticosteroid.
Current Topics in Medicinal Chemistry
Title:Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area
Volume: 17 Issue: 8
Author(s): Hana Cipcic Paljetak, Linda Tomaskovic, Mario Matijasic, Mirjana Bukvic, Andrea Fajdetic, Donatella Verbanac and Mihaela Peric
Affiliation:
Keywords: Macrolide Hybrid, Azalide, Antibacterial, Antimalarial, Anti-inflammatory, Quinolone, Quinoline, Corticosteroid.
Abstract: Macrolides, polyketide natural products, and their 15-membered semi-synthetic derivatives are composed of substituted macrocyclic lactone ring and used primarily as potent antibiotics. Recently their usefulness was extended to antimalarial and anti-inflammatory area. Hybrid macrolides presented in this article are the next generation semi-synthetic compounds that combine pharmacophores from antibacterial, antimalarial and anti-inflammatory area with 14- and 15-membered azalide scaffolds. Antibacterial azalide hybrids with sulphonamides showed improved activity against resistant streptococci while quinolone conjugates demonstrated full coverage of respiratory pathogens including macrolide resistant strains and their efficacy was confirmed in mouse pneumonia model. Antimalarial macrolide hybrids, mainly involving (chloro)quinoline pharmacophores, showed outstanding activity against chloroquine resistant strains, favourable pharmacokinetics, promising in vivo efficacy as well as encouraging developmental potential. Anti-inflammatory hybrids were obtained by combining macrolides with corticosteroid and non-steroidal anti-inflammatory drugs. They were found active in in vivo animal models of locally induced inflammation, asthma, inflammatory bowel disease and rheumatoid arthritis and demonstrated improved safety over parent steroid drugs. Overall, macrolide hybrids possess significant potential to be developed as potent novel medicines in therapeutic areas of utmost pharmaceutical interest.
Export Options
About this article
Cite this article as:
Paljetak Cipcic Hana, Tomaskovic Linda, Matijasic Mario, Bukvic Mirjana, Fajdetic Andrea, Verbanac Donatella and Peric Mihaela, Macrolide Hybrid Compounds: Drug Discovery Opportunities in Anti- Infective and Anti-inflammatory Area, Current Topics in Medicinal Chemistry 2017; 17 (8) . https://dx.doi.org/10.2174/1568026616666160927160036
DOI https://dx.doi.org/10.2174/1568026616666160927160036 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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 the Synthesis and Development of Curcumin, its Combinations and Formulations and Curcumin-like Compounds as Anti-infective Agents
Current Medicinal Chemistry New Pharmacological Approaches to the Cholinergic System: An Overview on Muscarinic Receptor Ligands and Cholinesterase Inhibitors
Recent Patents on CNS Drug Discovery (Discontinued) Antihistamines as Important Tools for Regulating Inflammation
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Impact of COVID-19 Infection on Maternal and Neonatal Outcomes: A Review of 11078 Pregnancies Reported in the Literature
Current Women`s Health Reviews Treatment of Severe Cases of Pandemic (H1N1) 2009 Influenza: Review of Antivirals and Adjuvant Therapy
Recent Patents on Anti-Infective Drug Discovery Targets and Patented Drugs for Chemotherapy of Chagas Disease in the Last 15 Years-Period
Recent Patents on Anti-Infective Drug Discovery Drug Treatment of Eosinophilic Oesophagitis
Current Drug Metabolism SiRNA Mediated Gene Silencing: Hurdles, Strategies and Applications
Pharmaceutical Nanotechnology Bioactive Compounds in Some Culinary Aromatic Herbs and Their Effects on Human Health
Mini-Reviews in Medicinal Chemistry Recent Applications of Birch Reduction in Total Synthesis of Natural Products
Current Organic Chemistry Development of Safe and Economical Synthesis of Isoxazole
Letters in Organic Chemistry Endotoxin, TLR4 Signaling and Vascular Inflammation: Potential Therapeutic Targets in Cardiovascular Disease
Current Pharmaceutical Design Bronchiolitis, Bronchitis, Asthma Exacerbation, Bronchopneumonia, Pneumonia: A Didactic Stepwise Approach
Current Respiratory Medicine Reviews The Role of Vitamin D in Prevention and Treatment of Infection
Inflammation & Allergy - Drug Targets (Discontinued) The Adenosine A2b Receptor: Its Role in Inflammation
Endocrine, Metabolic & Immune Disorders - Drug Targets Occurrence, Structure Elucidation, Biosynthesis, Functions and Synthesis of Sphingadienes
Mini-Reviews in Organic Chemistry Strategies for Leukotriene Modulation in Dermatology: Current Evidence and Visionary Perspectives
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Probiotics: From Functional Foods to Pharmaceutical Products
Current Pharmaceutical Biotechnology Cyclophilins in Atherosclerosis: A New Therapeutic Target?
Current Pharmaceutical Design Pharmacokinetics and Systemic Activity of a New Patent of an Inhaled Corticosteroid/Long-Acting β2-Agonist Combination for Use in Asthma Therapy: Fluticasone Furoate/Vilanterol Trifenatate
Recent Patents on Inflammation & Allergy Drug Discovery