Abstract
Podophyllotoxin derivatives like etoposide 7a, etophos 7b, and teniposide 7c are used clinically as potent chemotherapeutic agents for a variety of tumors including small cell lung carcinoma, testicular cancer, and malignant lymphoma. These compounds derived from a series of modifications which converted podophyllotoxin 1a from an entity that interacted with tubulin and blocks mitosis to one that induced a block in late S or early G2 by interacting with topoisomerase II. Synthetic studies on podophyllotoxin derivatives can be divided in four general approaches (the oxo-ester route, the dihydroxy acid route, the tandem conjugate addition route and the Diels-Alder route). Albeit a number of synthetic sequences afforded products with excellent enantiopurities, the low overall yields still disqualify synthesis as an alternative for naturally produced materials. An alternative route based on the enzyme-catalyzed cyclization of synthetic intermediates to analogues of the podophyllotoxin family is being explored. Synthetic dibenzylbutanolides, which were revealed by biosynthetic studies to be the precursors of aryltetralin lignans, have been treated with enzymes derived from cell cultures of Podophyllum peltatum, Catharanthus roseus, Nicotiana sylvestris and Cassia didymobotrya. The ciclyzation process afforded however compounds with a different stereochemistry in the C ring. The obtainment of a novel compound with a benzylidenebenzylbutirolactone structure still leaves considerable scope for exploring biotransformations in order to obtain podophyllotoxin analogues via a combination of synthetic chemistry and biotechnological methods.
Keywords: aryltetralin lignans, podophyllotoxin derivatives, chemotherapeutic agents, tumors, cell lung carcinoma, testicular cancer, malignant lymphoma, topoisomerase II, podophyllum peltatum, catharanthus roseus, nicotiana sylvestris
Current Medicinal Chemistry
Title: Aryltetralin Lignans: Chemistry, Pharmacology and Biotransformations
Volume: 8 Issue: 11
Author(s): Bruno Botta, Giulliano Delle Monache, Domenico Misiti, Alberto Vitali and Giovanni Zappia
Affiliation:
Keywords: aryltetralin lignans, podophyllotoxin derivatives, chemotherapeutic agents, tumors, cell lung carcinoma, testicular cancer, malignant lymphoma, topoisomerase II, podophyllum peltatum, catharanthus roseus, nicotiana sylvestris
Abstract: Podophyllotoxin derivatives like etoposide 7a, etophos 7b, and teniposide 7c are used clinically as potent chemotherapeutic agents for a variety of tumors including small cell lung carcinoma, testicular cancer, and malignant lymphoma. These compounds derived from a series of modifications which converted podophyllotoxin 1a from an entity that interacted with tubulin and blocks mitosis to one that induced a block in late S or early G2 by interacting with topoisomerase II. Synthetic studies on podophyllotoxin derivatives can be divided in four general approaches (the oxo-ester route, the dihydroxy acid route, the tandem conjugate addition route and the Diels-Alder route). Albeit a number of synthetic sequences afforded products with excellent enantiopurities, the low overall yields still disqualify synthesis as an alternative for naturally produced materials. An alternative route based on the enzyme-catalyzed cyclization of synthetic intermediates to analogues of the podophyllotoxin family is being explored. Synthetic dibenzylbutanolides, which were revealed by biosynthetic studies to be the precursors of aryltetralin lignans, have been treated with enzymes derived from cell cultures of Podophyllum peltatum, Catharanthus roseus, Nicotiana sylvestris and Cassia didymobotrya. The ciclyzation process afforded however compounds with a different stereochemistry in the C ring. The obtainment of a novel compound with a benzylidenebenzylbutirolactone structure still leaves considerable scope for exploring biotransformations in order to obtain podophyllotoxin analogues via a combination of synthetic chemistry and biotechnological methods.
Export Options
About this article
Cite this article as:
Botta Bruno, Monache Delle Giulliano, Misiti Domenico, Vitali Alberto and Zappia Giovanni, Aryltetralin Lignans: Chemistry, Pharmacology and Biotransformations, Current Medicinal Chemistry 2001; 8 (11) . https://dx.doi.org/10.2174/0929867013372292
DOI https://dx.doi.org/10.2174/0929867013372292 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Discovery of Novel CYP17 Inhibitors for the Treatment of Prostate Cancer with Structure-Based Drug Design
Letters in Drug Design & Discovery Urine Cells-derived iPSCs: An Upcoming Frontier in Regenerative Medicine
Current Medicinal Chemistry Genetic Polymorphisms of Drug Metabolising Enzymes and Drug Transporters in Relation to Cancer Risk
Current Cancer Therapy Reviews Recent Advances in Understanding Hormonal Therapy Resistant Prostate Cancer
Current Cancer Drug Targets Colchicine, Biologic Agents and More for the Treatment of Familial Mediterranean Fever. The Old, the New, and the Rare
Current Medicinal Chemistry Targeting Apoptotic Pathways in Myocardial Infarction: Attenuated by Phytochemicals
Cardiovascular & Hematological Agents in Medicinal Chemistry Analytical Approaches for Assaying Metallodrugs in Biological Samples: Recent Methodological Developments and Future Trends
Current Drug Metabolism Aromatase, Estrogens and Testicular Germ Cell Development
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Combinations of Plant Polyphenols & Anti-Cancer Molecules: A Novel Treatment Strategy for Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Serum Tumor Markers in Stage I-II Breast Cancer
Medicinal Chemistry Hormones and their Receptors Bridge Fat and Bone Metabolisms
Current Signal Transduction Therapy Drug Delivery Systems and Combination Therapy by Using Vinca Alkaloids
Current Topics in Medicinal Chemistry Membrane Disrupting Lytic Peptides for Cancer Treatments
Current Pharmaceutical Design Phosphodiesterase Type 5 Inhibitors: Unmet Needs
Current Pharmaceutical Design Oxidative Stress and NAD+ in Ischemic Brain Injury: Current Advances and Future Perspectives
Current Medicinal Chemistry Application of Recombinant and Non-Recombinant Peptides in the Determination of Tumor Response to Cancer Therapy
Current Pharmaceutical Biotechnology Bleomycin and its Role in Inducing Apoptosis and Senescence in Lung Cells - Modulating Effects of Caveolin-1
Current Cancer Drug Targets The Role of Oxidative Stress and Anti-Oxidant Treatment in Platinum- Induced Peripheral Neurotoxicity
Current Cancer Drug Targets Steroid Regulation of Drug-Metabolizing Cytochromes P450
Current Drug Metabolism Prophylaxis with Bacopa monnieri Attenuates Acrylamide Induced Neurotoxicity and Oxidative Damage via Elevated Antioxidant Function
Central Nervous System Agents in Medicinal Chemistry