Abstract
Herein is described in silico repositioning, design, synthesis, biological evaluation and structure-activity relationship (SAR) of an original class of anti-inflammatory agents based on a polyaromatic pharmacophore structurally related to bisacodyl (BSL) drug used in therapeutic as laxative. We describe the potential of TOMOCOMD-CARDD methods to find out new anti-inflammatory drug-like agents from a diverse series of compounds using the total and local atom based bilinear indices as molecular descriptors. The models obtained were validated by biological studies, identifying BSL as the first anti-inflammatory lead-like using in silico repurposing from commercially available drugs. Several biological in vitro and in vivo assays were performed in order to understand its mechanism of action. A set of analogues of BSL was prepared using low-cost synthetic procedures and further biologically investigated in zebrafish models. Compound 5c and 7e exhibited the best antiinflammatory activities and represent new promising anti-inflammatory agents for further preclinical development.
Keywords: TOMOCOMD-CARDD Software, Atom-based bilinear indices, Anti-inflammatory database, Bisacodyl, Repurposing, Diarylmethylpyridines, Anti-inflammatory assay.
Current Topics in Medicinal Chemistry
Title:Fishing Anti-Inflammatories from Known Drugs: In Silico Repurposing, Design, Synthesis and Biological Evaluation of Bisacodyl Analogues
Volume: 17 Issue: 25
Author(s): Maité Sylla-Iyarreta Veitía*, Dany Siverio Mota, Vanessa Lerari, Marta Marín, Rosa M. Giner, Liliana Vicet Muro, Yankier Rivero Guerra, Françoise Dumas, Clotilde Ferroud, Peter A. M. de Witte, Alexander D. Crawford, Vicente J. Arán and Yovani Marrero Ponce
Affiliation:
- Equipe de chimie moléculaire, Laboratoire Chimie Moléculaire, génie des procédés chimiques et énergétiques (CMGPCE), EA 7341- Conservatoire National des Arts et Métiers, 2 rue Conté, 75003, Paris,France
Keywords: TOMOCOMD-CARDD Software, Atom-based bilinear indices, Anti-inflammatory database, Bisacodyl, Repurposing, Diarylmethylpyridines, Anti-inflammatory assay.
Abstract: Herein is described in silico repositioning, design, synthesis, biological evaluation and structure-activity relationship (SAR) of an original class of anti-inflammatory agents based on a polyaromatic pharmacophore structurally related to bisacodyl (BSL) drug used in therapeutic as laxative. We describe the potential of TOMOCOMD-CARDD methods to find out new anti-inflammatory drug-like agents from a diverse series of compounds using the total and local atom based bilinear indices as molecular descriptors. The models obtained were validated by biological studies, identifying BSL as the first anti-inflammatory lead-like using in silico repurposing from commercially available drugs. Several biological in vitro and in vivo assays were performed in order to understand its mechanism of action. A set of analogues of BSL was prepared using low-cost synthetic procedures and further biologically investigated in zebrafish models. Compound 5c and 7e exhibited the best antiinflammatory activities and represent new promising anti-inflammatory agents for further preclinical development.
Export Options
About this article
Cite this article as:
Veitía Sylla-Iyarreta Maité *, Mota Siverio Dany , Lerari Vanessa , Marín Marta , Giner M. Rosa , Muro Vicet Liliana , Guerra Rivero Yankier , Dumas Françoise , Ferroud Clotilde , de Witte A. M. Peter , Crawford D. Alexander , Arán J. Vicente and Ponce Marrero Yovani , Fishing Anti-Inflammatories from Known Drugs: In Silico Repurposing, Design, Synthesis and Biological Evaluation of Bisacodyl Analogues, Current Topics in Medicinal Chemistry 2017; 17 (25) . https://dx.doi.org/10.2174/1568026617666170817161953
DOI https://dx.doi.org/10.2174/1568026617666170817161953 |
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
-
Nanoparticulate Drug Delivery Systems for Treatment of Hepatocellular Carcinoma
Current Cancer Therapy Reviews Cyclodextrin-based Polymeric Nanoparticles as Efficient Carriers for Anticancer Drugs
Current Pharmaceutical Biotechnology TRYCAT Pathways Link Peripheral Inflammation, Nicotine, Somatization and Depression in the Etiology and Course of Parkinson’s Disease
CNS & Neurological Disorders - Drug Targets The Role of B Cell Receptor Stimulation in CLL Pathogenesis
Current Pharmaceutical Design Genomic and Pharmacogenomic Biomarkers of Parkinson’s Disease
Current Drug Metabolism Mechanism of Action of Flavonoids in Prevention of Inflammation- Associated Skin Cancer
Current Medicinal Chemistry Bcl-2 Proteins: Targets and Tools for Chemosensitisation of Tumor Cells
Current Medicinal Chemistry - Anti-Cancer Agents Adenosine A<sub>3</sub> Receptor: A promising therapeutic target in cardiovascular disease
Current Cardiology Reviews Ultra-deformable Liposomes as Flexible Nanovesicular Carrier to Penetrate Versatile Drugs Transdermally
Nanoscience & Nanotechnology-Asia 5-Aryl-1,3,4-Thiadiazole-Based Hydroxamic Acids as Histone Deacetylase Inhibitors and Antitumor Agents: Synthesis, Bioevaluation and Docking Study
Medicinal Chemistry The Role for Oxidative Stress in Aberrant DNA Methylation in Alzheimer’s Disease
Current Alzheimer Research Knocking Down Gene Expression with Dendritic Vectors
Mini-Reviews in Medicinal Chemistry Betulin-Betulinic Acid Natural Product Based Analogs as Anti-Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry GEMSP: A New Therapeutic Approach to Multiple Sclerosis
Central Nervous System Agents in Medicinal Chemistry Peptides for Diagnosis and Treatment of Colorectal Cancer
Current Medicinal Chemistry Recent Advances on Liquid Chromatographic and Mass Spectrometric Analysis of Selective Estrogen Receptor Modulators (SERMs) in Biological Fluids
Current Chromatography Anti-Angiogenic Peptides for Cancer Therapeutics
Current Pharmaceutical Biotechnology Lipoamino Acids as Major Components of Absorption Promoters in Drug Delivery
Current Topics in Medicinal Chemistry Tip60: Main Functions and Its Inhibitors
Mini-Reviews in Medicinal Chemistry Stem Cells and the Side Population Theory: A Critical Review
Current Tissue Engineering (Discontinued)