Abstract
Cancer is a multifactorial disease and most of its types still remain incurable, in spite of enormous efforts to explicate various tumor pathophysiology. The anti-cancer drug discovery paradigm “one-compound-one-target” has failed and subsequently shifted to two-drug cocktail and recently the “multi-target approach” in order to design and develop agents able to act simultaneously on multiple intracellular constituents and signaling pathways. Novel hybrid compounds are now designed by incorporating two covalently linked independently acting pharmacores, each efficient at combating cancer. They can deliver synergistic effects from the dual action of both independently acting moieties by interacting with multiple targets. These composite molecules are also less prone to drug resistance, leading to an improved pharmacological potency than each individual moiety. As indole nucleus is a central component of many natural and synthetic molecules with extensive biological activity, this review incorporates a variety of such hybrid compounds with indole moiety as one of the active units, where better therapeutic effect has been successfully achieved, by either simultaneous or sequential action of individual functional pharmacore. The current limitations and challenges encountered in the development of these hybrid agents are also discussed.
Keywords: Cancer, Tumor-microenvironment, Indole, Hybrid, Multi-target, Challenges.
Current Topics in Medicinal Chemistry
Title:Multi-Target Directed Indole Based Hybrid Molecules in Cancer Therapy : An Up-To-Date Evidence-Based Review
Volume: 17 Issue: 9
Author(s): Dhanya Sunil and Pooja R. Kamath
Affiliation:
Keywords: Cancer, Tumor-microenvironment, Indole, Hybrid, Multi-target, Challenges.
Abstract: Cancer is a multifactorial disease and most of its types still remain incurable, in spite of enormous efforts to explicate various tumor pathophysiology. The anti-cancer drug discovery paradigm “one-compound-one-target” has failed and subsequently shifted to two-drug cocktail and recently the “multi-target approach” in order to design and develop agents able to act simultaneously on multiple intracellular constituents and signaling pathways. Novel hybrid compounds are now designed by incorporating two covalently linked independently acting pharmacores, each efficient at combating cancer. They can deliver synergistic effects from the dual action of both independently acting moieties by interacting with multiple targets. These composite molecules are also less prone to drug resistance, leading to an improved pharmacological potency than each individual moiety. As indole nucleus is a central component of many natural and synthetic molecules with extensive biological activity, this review incorporates a variety of such hybrid compounds with indole moiety as one of the active units, where better therapeutic effect has been successfully achieved, by either simultaneous or sequential action of individual functional pharmacore. The current limitations and challenges encountered in the development of these hybrid agents are also discussed.
Export Options
About this article
Cite this article as:
Sunil Dhanya and Kamath R. Pooja, Multi-Target Directed Indole Based Hybrid Molecules in Cancer Therapy : An Up-To-Date Evidence-Based Review, Current Topics in Medicinal Chemistry 2017; 17 (9) . https://dx.doi.org/10.2174/1568026616666160927150839
DOI https://dx.doi.org/10.2174/1568026616666160927150839 |
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
-
Novel Molecular Targets in Cancer Chemotherapy Waiting for Discovery
Current Medicinal Chemistry - Anti-Cancer Agents Aryltetralin Lignans: Chemistry, Pharmacology and Biotransformations
Current Medicinal Chemistry Natural Products and their Analogues as Efficient Anticancer Drugs
Mini-Reviews in Medicinal Chemistry Meet Our Editorial Board Member
Current Drug Targets Biochemical Mechanisms of Cisplatin Cytotoxicity
Anti-Cancer Agents in Medicinal Chemistry Of Man in Mouse: Modelling Human Cancer Genotype-Phenotype Correlations in Mice
Current Genomics Nutraceuticals - An Emerging Era in the Treatment and Prevention of Cardiovascular Diseases
Current Pharmaceutical Biotechnology Dual Acting Isatin-heterocyclic Hybrids: Recent Highlights as Promising Pharmacological Agents
Letters in Drug Design & Discovery Recent Advances In Developing Novel Anti-Cancer Drugs Targeting Tumor Hypoxic and Acidic Microenvironments
Recent Patents on Anti-Cancer Drug Discovery Cancer Bioinformatics for Updating Anticancer Drug Developments and Personalized Therapeutics
Reviews on Recent Clinical Trials Immunogenetic Mechanisms Leading to Thyroid Autoimmunity: Recent Advances in Identifying Susceptibility Genes and Regions
Current Genomics Biochemical and Structural Insights into the Eukaryotic Translation Initiation Factor eIF4E
Current Protein & Peptide Science Several Classes of Natural Products with Metal ion Chelating Ability
Current Organic Chemistry Regulation of Gene Expression by Progesterone in Cancer Cells: Effects on Cyclin D1, EGFR and VEGF
Mini-Reviews in Medicinal Chemistry Reduction of Doxorubicin-Induced Cardiotoxicity Using Nanocarriers: A Review
Current Drug Metabolism Dimethyl Sulfoxide as an Excitatory Modulator and its Possible Role in Cancer Pain Management
Inflammation & Allergy - Drug Targets (Discontinued) Role of Lycopene in the Control of ROS-Mediated Cell Growth: Implications in Cancer Prevention
Current Medicinal Chemistry Extraction Methods for Downstream Processing of Bioactive Compounds From Natural Sources
Current Biochemical Engineering (Discontinued) Patent Selections
Recent Patents on Drug Delivery & Formulation Regulation of Apoptosis and Activity of the Osteoclast
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued)