Abstract
The indole scaffold probably represents one of the most important structural subunits for the discovery of new drug candidates. The demonstration that many alkaloids contain the indole nucleus, the recognition of the importance of essential amino acid tryptophan in human nutrition and the discovery of plant hormones served to bring about a massive search on indole chemistry, giving rise to a vast number of biologically active natural and synthetic products, with a wide range of therapeutic targets, such as anti-inflammatories, phosphodiesterase inhibitors, 5-hydroxytryptamine receptor agonists and antagonists, cannabinoid receptors agonists and HMG-CoA reductase inhibitors. Many of these target-receptors belong to the class of GPCRs (integral membrane G-protein coupled receptors) and possess a conserved binding pocket that is recognized by the indole scaffold in a “common” complementary binding domain, explaining the great number of drugs that contain the indole substructure, such as indomethacin, ergotamine, frovatriptan, ondansetron, tadalafil, among many others.
Keywords: Indole scaffold, privileged structure, GPCR, bioisosterism, drug discovery
Mini-Reviews in Medicinal Chemistry
Title: From Nature to Drug Discovery: The Indole Scaffold as a ‘Privileged Structure’
Volume: 9 Issue: 7
Author(s): Fernando Rodrigues de Sa Alves, Eliezer J. Barreiro and Carlos Alberto Manssour Fraga
Affiliation:
Keywords: Indole scaffold, privileged structure, GPCR, bioisosterism, drug discovery
Abstract: The indole scaffold probably represents one of the most important structural subunits for the discovery of new drug candidates. The demonstration that many alkaloids contain the indole nucleus, the recognition of the importance of essential amino acid tryptophan in human nutrition and the discovery of plant hormones served to bring about a massive search on indole chemistry, giving rise to a vast number of biologically active natural and synthetic products, with a wide range of therapeutic targets, such as anti-inflammatories, phosphodiesterase inhibitors, 5-hydroxytryptamine receptor agonists and antagonists, cannabinoid receptors agonists and HMG-CoA reductase inhibitors. Many of these target-receptors belong to the class of GPCRs (integral membrane G-protein coupled receptors) and possess a conserved binding pocket that is recognized by the indole scaffold in a “common” complementary binding domain, explaining the great number of drugs that contain the indole substructure, such as indomethacin, ergotamine, frovatriptan, ondansetron, tadalafil, among many others.
Export Options
About this article
Cite this article as:
de Sa Alves Rodrigues Fernando, Barreiro J. Eliezer and Manssour Fraga Alberto Carlos, From Nature to Drug Discovery: The Indole Scaffold as a ‘Privileged Structure’, Mini-Reviews in Medicinal Chemistry 2009; 9 (7) . https://dx.doi.org/10.2174/138955709788452649
DOI https://dx.doi.org/10.2174/138955709788452649 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...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
Related Articles
-
Coagulopathy in Type 2 Diabetes Mellitus: Pathological Mechanisms and the Role of Factor XIII-A Single Nucleotide Polymorphisms
Current Diabetes Reviews Cardiac Stem Cell-Based Myocardial Regeneration: Towards a Translational Approach
Cardiovascular & Hematological Agents in Medicinal Chemistry Cell Adhesion Molecules as Pharmaceutical Target in Atherosclerosis
Mini-Reviews in Medicinal Chemistry Heart Transplantation for Congenital Heart Disease in the First Year of Life
Current Cardiology Reviews Disruption of Circadian Rhythms and Sleep on Critical Illness and the Impact on Cardiovascular Events
Current Pharmaceutical Design Monitoring and Surveillance of Obesity in the United States
Current Nutrition & Food Science Novel Antidepressant Drugs, Arterial Hypertension and Cardiovascular Disease
Recent Patents on Cardiovascular Drug Discovery Cardiovascular Magnetic Resonance Imaging clarifies cardiac pathophysiology in early, asymptomatic diffuse systemic sclerosis
Inflammation & Allergy - Drug Targets (Discontinued) Induced Pluripotent Stem Cells (iPSCs) Derived from Different Cell Sources and their Potential for Regenerative and Personalized Medicine
Current Molecular Medicine Vaccine Development for Group A Streptococcus Infections and Associated Diseases
Current Drug Targets Atherosclerosis as an Inflammatory Disease
Current Pharmaceutical Design The Renal Epithelial Sodium Channel: Genetic Heterogeneity and Implications for the Treatment of High Blood Pressure
Current Pharmaceutical Design Advanced In Silico Approaches for Drug Discovery: Mining Information from Multiple Biological and Chemical Data Through mtk- QSBER and pt-QSPR Strategies
Current Medicinal Chemistry Incretin-Based Therapies, Glucometabolic Health and Endovascular Inflammation
Current Pharmaceutical Design Supramolecular Chiro-Biomedical Aspect of β-Blockers in Drug Development
Current Drug Targets Drug-Lipid Membrane Interaction Mechanisms Revealed Through Molecular Simulations
Current Physical Chemistry Targeting Inhibition of COX-2: A Review of Patents, 2002 - 2006
Recent Patents on Inflammation & Allergy Drug Discovery Implications of Pharmacogenetics for Oral Anticoagulants Metabolism
Current Drug Metabolism Anti-Biofilm Strategies and the Need for Innovations in Wound Care
Recent Patents on Anti-Infective Drug Discovery Risk Scores for Patients with Chest Pain: Evaluation in the Emergency Department
Current Cardiology Reviews