Abstract
A major impediment for cancer chemotherapy is the development of multidrug-resistance (MDR). Continuous use of chemotherapeutic drugs during cancer therapy induces the expression of PGlycoprotein (P-gp, MDR1), an ATP dependant transporter, which in turn reduces the intracellular accumulation of chemotherapeutic drugs leading to MDR. Extensive research over the years has identified several potential P-gp inhibitors, both synthetic as well as natural origin, to overcome the MDR during cancer chemotherapy. In this review, we discuss the cellular pathways involved and transcription factors regulating the expression of P-gp. A number of phytochemicals are reported to inhibit P-gp activity and MDR1 expression; the structure-activity relationship (SAR) among the phytochemicals for P-gp inhibition and the effect of these phytochemicals on cellular signaling pathways regulating P-gp expression are discussed in detail. Moreover, structural biology and mutagenesis studies on P-gp along with docking studies throw light on the structural requirements for P-gp inhibition. Insight provided in the review about the phytochemicals molecular mechanism and SAR could catalyze the design of potent P-gp inhibitors in the future and could help to overcome MDR in cancer chemotherapy.
Keywords: Chemotherapy, Multidrug resistance (MDR), P-glycoprotein (P-gp), Phytochemicals, Structure Activity Relationship.
Current Topics in Medicinal Chemistry
Title:P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design
Volume: 16 Issue: 22
Author(s): Safiulla Basha Syed and Mohane Selvaraj Coumar
Affiliation:
Keywords: Chemotherapy, Multidrug resistance (MDR), P-glycoprotein (P-gp), Phytochemicals, Structure Activity Relationship.
Abstract: A major impediment for cancer chemotherapy is the development of multidrug-resistance (MDR). Continuous use of chemotherapeutic drugs during cancer therapy induces the expression of PGlycoprotein (P-gp, MDR1), an ATP dependant transporter, which in turn reduces the intracellular accumulation of chemotherapeutic drugs leading to MDR. Extensive research over the years has identified several potential P-gp inhibitors, both synthetic as well as natural origin, to overcome the MDR during cancer chemotherapy. In this review, we discuss the cellular pathways involved and transcription factors regulating the expression of P-gp. A number of phytochemicals are reported to inhibit P-gp activity and MDR1 expression; the structure-activity relationship (SAR) among the phytochemicals for P-gp inhibition and the effect of these phytochemicals on cellular signaling pathways regulating P-gp expression are discussed in detail. Moreover, structural biology and mutagenesis studies on P-gp along with docking studies throw light on the structural requirements for P-gp inhibition. Insight provided in the review about the phytochemicals molecular mechanism and SAR could catalyze the design of potent P-gp inhibitors in the future and could help to overcome MDR in cancer chemotherapy.
Export Options
About this article
Cite this article as:
Syed Basha Safiulla and Coumar Selvaraj Mohane, P-Glycoprotein Mediated Multidrug Resistance Reversal by Phytochemicals: A Review of SAR & Future Perspective for Drug Design, Current Topics in Medicinal Chemistry 2016; 16 (22) . https://dx.doi.org/10.2174/1568026616666160212123814
DOI https://dx.doi.org/10.2174/1568026616666160212123814 |
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
-
Editorial [Hot Topic: New Developments in the Medicinal Chemistry of Vanilloid TRPV1 and Related Receptors (Guest Editor: Arpad Szallasi)]
Current Topics in Medicinal Chemistry Evolution of Ipsilateral Head and Neck Radiotherapy
Current Cancer Therapy Reviews Targeting Inhibitor of Apoptosis Proteins (IAPs) for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry The Vitamin D/CYP24A1 Story in Cancer
Anti-Cancer Agents in Medicinal Chemistry Synthesis and Bioactivity of (R)-Ricinoleic Acid Derivatives: A Review
Current Medicinal Chemistry Expression, Regulation, and Role of an Oligopeptide Transporter: PEPT1 in Tumors
Current Medicinal Chemistry Role of Thymidine Phosphorylase in Biomodulation of Fluoropyrimidines
Current Pharmaceutical Biotechnology Exploring the Mitochondrial Apoptotic Cell Death Landscape and Associated Components Serving as Molecular Targets, Primarily for Synthetic and Natural Drugs Targeting Oncology Therapeutics
Current Molecular Pharmacology Can Dietary Antioxidants Reduce the Incidence of Brain Tumors?
Current Drug Metabolism Inhibitors of ABL and the ABL-T315I Mutation
Current Topics in Medicinal Chemistry The Role of Proteomics in Osteoarthritis Pathogenesis Research
Current Drug Targets Proteomics in the Search for Biomarkers of Animal Cancer
Current Protein & Peptide Science Angiogenesis and Angiogenesis Inhibitors: a New Potential Anticancer Therapeutic Strategy
Current Drug Targets - Immune, Endocrine & Metabolic Disorders Identification of Biomarkers and Functional Modules from Genomic Data in Stage-wise Breast Cancer
Current Bioinformatics Meet the Editorial Board Member
Recent Advances in Drug Delivery and Formulation Drug Analogs of COX-2 Selective Inhibitors Lumiracoxib and Valdecoxib Derived from in silico Search and Optimization
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Role of ABC Transporters in Veterinary Medicine: Pharmaco- Toxicological Implications
Current Medicinal Chemistry Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics HGF and RhoGTPases in Cancer Cell Motility
Current Signal Transduction Therapy Anti-inflammatory Phytochemicals for Chemoprevention of Colon Cancer
Current Cancer Drug Targets