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
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...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
- 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
-
Lipases in Medicine: An Overview
Mini-Reviews in Medicinal Chemistry Homeostasis and Compensatory Homeostasis: Bridging Western Medicine and Traditional Chinese Medicine
Current Cardiology Reviews Biological Roles of the Eclectic Chromogranin-A-derived Peptide Catestatin
Current Medicinal Chemistry The Common Mycobacterial Antigens and their Importance in the Treatment of Disease
Current Pharmaceutical Design Contemporary Risk Assessment and Cardiovascular Outcomes in Peripheral Arterial Disease
Cardiovascular & Hematological Disorders-Drug Targets Nano Approaches to Enhance Pharmacokinetic and Pharmacodynamic Activity of Plant Origin Drugs
Current Nanoscience Protective Effect of Natural Antioxidants on Heart Against Ischemia-Reperfusion Damage
Current Pharmaceutical Biotechnology Rational Basis for Nutraceuticals in the Treatment of Glaucoma
Current Neuropharmacology Steroid Hybrid Systems: New Molecular Entities with Potential Therapeutical Spectrum
Current Drug Therapy Flavonoid Antioxidants
Current Medicinal Chemistry Impact of Traditional Therapies and Biologics on Cardiovascular Diseases in Rheumatoid Arthritis
Current Vascular Pharmacology Advances in Irrigated Tip Catheter Technology for Treatment of Cardiac Arrhythmias
Recent Patents on Cardiovascular Drug Discovery The Effect of SEX/Gender on Cardiovascular Pharmacology
Current Pharmaceutical Design Diagnosis and Management of Heart Failure with Preserved Ejection Fraction: 10 Key Lessons
Current Cardiology Reviews Irbesartan and Hydrochlorothiazide Association in the Treatment of Hypertension
Current Vascular Pharmacology Alzheimers and Dementia in the Oldest-Old: A Century of Challenges
Current Alzheimer Research Knowledge and Perceptions Towards Cardiovascular Disease Prevention Among Patients with Type 2 Diabetes Mellitus: A Review of Current Assessments and Recommendations
Current Diabetes Reviews Prognostic Role of Sub-Clinical Hypothyroidism in Chronic Heart Failure Outpatients
Current Pharmaceutical Design Sodium-Proton Exchanger Isoform-1: Synthesis of a Potent Inhibitor Labeled with Deuterium and Carbon-14
Current Radiopharmaceuticals Statistically Designed Extraction of Herbs Using Ultrasound Waves: A Review
Current Pharmaceutical Design