Abstract
Over 200 derivatives have been obtained through chemo-enzymatic transformation of the taxanes derived from cell cultures of Taxus chinensis. The reversal activity towards MDR tumor cells and cyto-toxicity of most these compounds were evaluated, and several derivatives exhibited powerful MDR reversal activity. The substrate-specificities of the two most important biotransformation reactions-C-7β and 9α hydroxylations, were investigated and preliminarily concluded. In addition, some key intermediates in hypothetically biosynthetic pathway of taxoid were obtained. These results indicate that biotransformation combined with chemical transformation is a powerful approach to structural diversification of natural products, lead compound discovery and the study on the structure activity relationships of the derivatives. Moreover, biotransformation may mimic some steps in biosynthetic pathway of natural products and provide useful hints as to their biogenetic study.
Keywords: Taxane, reversal activity, MDR tumor cells, enzymatic transformation, chemical transformation
Current Topics in Medicinal Chemistry
Title: Chemo-Enzymatic Transformation of Taxanes and their Reversal Activity towards MDR Tumor Cells
Volume: 9 Issue: 17
Author(s): Jungui Dai
Affiliation:
Keywords: Taxane, reversal activity, MDR tumor cells, enzymatic transformation, chemical transformation
Abstract: Over 200 derivatives have been obtained through chemo-enzymatic transformation of the taxanes derived from cell cultures of Taxus chinensis. The reversal activity towards MDR tumor cells and cyto-toxicity of most these compounds were evaluated, and several derivatives exhibited powerful MDR reversal activity. The substrate-specificities of the two most important biotransformation reactions-C-7β and 9α hydroxylations, were investigated and preliminarily concluded. In addition, some key intermediates in hypothetically biosynthetic pathway of taxoid were obtained. These results indicate that biotransformation combined with chemical transformation is a powerful approach to structural diversification of natural products, lead compound discovery and the study on the structure activity relationships of the derivatives. Moreover, biotransformation may mimic some steps in biosynthetic pathway of natural products and provide useful hints as to their biogenetic study.
Export Options
About this article
Cite this article as:
Dai Jungui, Chemo-Enzymatic Transformation of Taxanes and their Reversal Activity towards MDR Tumor Cells, Current Topics in Medicinal Chemistry 2009; 9 (17) . https://dx.doi.org/10.2174/156802609789941924
DOI https://dx.doi.org/10.2174/156802609789941924 |
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
-
Targeting Vascular Niche by Parathyroid Hormone
Current Medicinal Chemistry Investigational Selective Melatoninergic Ligands for Receptor Subtype MT2
Mini-Reviews in Medicinal Chemistry Molecular Fundamentals and Rationale for Immunotherapy in Metastatic Melanoma Treatment
Clinical Cancer Drugs Sleep and COPD
Current Respiratory Medicine Reviews High-Throughput Functional Genomic Methods to Analyze the Effects of Dietary Lipids
Current Pharmaceutical Biotechnology Synthesis, Spectral Characterization, Antibacterial and Anticancer Activity of some Titanium Complexes
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Applications of Nanoemulsion Based Drug Delivery Systems: A Review of Patents in Last Two Decades
Recent Patents on Drug Delivery & Formulation Cdc42 Signaling Pathway Inhibition as a Therapeutic Target in Ras- Related Cancers
Current Medicinal Chemistry Hepatic Cytochrome P450 Regulation in Disease States
Current Drug Metabolism Scope and Limitations of The Co-Drug Approach to Topical Drug Delivery
Current Pharmaceutical Design Intrinsic Disorder-based Protein Interactions and their Modulators
Current Pharmaceutical Design Molecularly Imprinted Polymers: Novel Discovery for Drug Delivery
Current Drug Delivery Effect of Administration Route on the Biodistribution and Shedding of Replication-Deficient AAV2: A Qualitative Modelling Approach
Current Gene Therapy The Wnt Pathway: Emerging Anticancer Strategies
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Anthocyanins as a Potential Therapy for Diabetic Retinopathy
Current Medicinal Chemistry Absorption, Pharmacokinetics and Disposition Properties of Solid Lipid Nanoparticles (SLNs)
Current Drug Metabolism Microfluidic Hydrodynamic Cell Separation: A Review
Micro and Nanosystems Diverse Mechanisms of AKT Pathway Activation in Human Malignancy
Current Cancer Drug Targets Patent Selections
Recent Patents on Medical Imaging Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies Across Caco-2 Cells
Current Drug Delivery