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Journal of Oncology Practice Dec 2016
Topics: Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Etoposide; Humans; Testicular Neoplasms
PubMed: 27650845
DOI: 10.1200/JOP.2016.017137 -
Phytochemistry Dec 2021Wild chervil (Anthriscus sylvestris) is a widespread, wild-growing herbaceous plant from Apiaceae family, known for high content of lignans related to podophyllotoxin,...
Wild chervil (Anthriscus sylvestris) is a widespread, wild-growing herbaceous plant from Apiaceae family, known for high content of lignans related to podophyllotoxin, and thus representing a promising new source for their industrial isolation. The data on detailed chemical profile of A. sylvestris lignans are still lacking. By combining fractionation with non-targeted LC-DAD-ESI-MS/MS metabolite profiling, we have identified, fully or tentatively, 46 lignans, 12 of which were never reported in A. sylvestris and 19 in any biological source. The dominant lignans were found to be nemerosin, yatein, deoxypodophyllotoxin, podophyllotoxin, podophyllotoxone and guayadequiol. In addition to well-known dibenzylbutyrolactones, aryltetralins and 7-oxygenated aryltetralins, we found several oxygenated lignan classes previously undescribed in A. sylvestris - 7-hydroxy, 7-oxo and 8-hydroxydibenzylbutyrolactones, a 7'-oxotetrahydrofuran and a 7-hydroxyarylnaphthalene. To facilitate future rapid classification and identification of lignans in raw extracts, UV, MS and NMR spectral features of different lignan classes are described.
Topics: Apiaceae; Lignans; Plant Extracts; Podophyllotoxin; Tandem Mass Spectrometry
PubMed: 34560578
DOI: 10.1016/j.phytochem.2021.112958 -
Bioorganic Chemistry Jul 2023The DNA topoisomerase enzymes are widely distributed throughout all spheres of life and are necessary for cell function. Numerous antibacterial and cancer... (Review)
Review
The DNA topoisomerase enzymes are widely distributed throughout all spheres of life and are necessary for cell function. Numerous antibacterial and cancer chemotherapeutic drugs target the various topoisomerase enzymes because of their roles in maintaining DNA topology during DNA replication and transcription. Agents derived from natural products, like anthracyclines, epipodophyllotoxins and quinolones, have been widely used to treat a variety of cancers. A very active field of fundamental and clinical research is the selective targeting of topoisomerase II enzymes for cancer treatment. This thematic review summarizes the recent advances in the anticancer activity of the most potent topoisomerase II inhibitors (anthracyclines, epipodophyllotoxins and fluoroquinolones) their modes of action, and structure-activity relationships (SARs) organized chronologically in the last ten years from 2013 to 2023. The review also highlights the mechanism of action and SARs of promising new topoisomerase II inhibitors.
Topics: Topoisomerase II Inhibitors; Antineoplastic Agents; Antibiotics, Antineoplastic; DNA Topoisomerases, Type II; Podophyllotoxin; Anthracyclines; Topoisomerase I Inhibitors
PubMed: 37094479
DOI: 10.1016/j.bioorg.2023.106548 -
Pharmaceutical Biology Dec 2024Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.
CONTEXT
Podophyllotoxin (PPT) derivatives, used in cancer therapy, require development toward enhanced efficacy and reduced toxicity.
OBJECTIVE
This study synthesizes PPT derivatives to assess their anticancer activities.
MATERIALS AND METHODS
Compounds E1-E16 antiproliferative activity was tested against four human cancer cell lines (H446, MCF-7, HeLa, A549) and two normal cell lines (L02, BEAS-2B) using the CCK-8 assay. The effects of compound on A549 cell growth were evaluated through molecular docking, assays (flow cytometry, wound healing, Transwell, colony formation, Western blot), and tests in female BALB/c nude mice treated with (2 and 4 mg/kg). (4 mg/kg) significantly reduced xenograft tumor growth compared to the DMSO control group.
RESULTS
Among the 16 PPT derivatives tested for cytotoxicity, exhibited potent effects against A549 cells (IC: 0.35 ± 0.13 µM) and exceeded the reference drugs PPT and etoposide to inhibit the growth of xenograft tumours. -induced cell cycle arrest in the S and G2/M phases accelerated tubulin depolymerization and triggered apoptosis and mitochondrial depolarization while regulating the expression of apoptosis-related proteins and effectively inhibited cell migration and invasion, suggesting a potential to limit metastasis. Molecular docking showed binding of to tubulin at the colchicine site and to Akt, with a consequent down-regulation of PI3K/Akt pathway proteins.
DISCUSSION AND CONCLUSIONS
This research lays the groundwork for advancing cancer treatment through developing and using PPT derivatives. The encouraging results associated with call for extended research and clinical validation, leading to novel and more effective cancer therapies.
Topics: Mice; Animals; Humans; Female; Podophyllotoxin; Tubulin; Molecular Docking Simulation; Mice, Nude; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Drug Screening Assays, Antitumor; Antineoplastic Agents; Cell Proliferation; Cell Line, Tumor; Apoptosis; Tubulin Modulators
PubMed: 38393642
DOI: 10.1080/13880209.2024.2318350 -
Molecules (Basel, Switzerland) Dec 2022Plants containing podophyllotoxin and its analogues have been used as folk medicines for centuries. The characteristic chemical structures and strong biological... (Review)
Review
Plants containing podophyllotoxin and its analogues have been used as folk medicines for centuries. The characteristic chemical structures and strong biological activities of this class of compounds attracted attention worldwide. Currently, more than ninety natural podophyllotoxins were isolated, and structure modifications of these molecules were performed to afford a variety of derivatives, which offered optimized anti-tumor activity. This review summarized up to date reports on natural occurring podophyllotoxins and their sources, structural modification and biological activities. Special attention was paid to both structural modification and optimized antitumor activity. It was noteworthy that etoposide, a derivative of podophyllotoxin, could prevent cytokine storm caused by the recent SARS-CoV-2 viral infection.
Topics: Humans; Podophyllotoxin; Antineoplastic Agents, Phytogenic; Structure-Activity Relationship; COVID-19; SARS-CoV-2
PubMed: 36615496
DOI: 10.3390/molecules28010302 -
Viruses Oct 2016Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion...
Human cytomegalovirus is a ubiquitous β-herpesvirus that infects many different cell types through an initial binding to cell surface receptors followed by a fusion event at the cell membrane or endocytic vesicle. A recent high-throughput screen to identify compounds that block a step prior to viral gene expression identified podofilox as a potent and nontoxic inhibitor. Time-of-addition studies in combination with quantitative-PCR analysis demonstrated that podofilox limits an early step of virus entry at the cell surface. Podofilox was also able to drastically reduce infection by herpes simplex 1, an α-herpesvirus with a very similar entry process to CMV. Podofilox caused a reduced maximal plateau inhibition of infection by viruses with single step binding processes prior to fusion-like Newcastle disease virus, Sendai virus, and influenza A virus or viruses that enter via endocytosis like vesicular stomatitis virus and a clinical-like strain of CMV. These results indicate that microtubules appear to be participating in the post-binding step of virus entry including the pre- and post-penetration events. Modulation of the plasma membrane is required to promote virus entry for herpesviruses, and that podofilox, unlike colchicine or nocodazole, is able to preferentially target microtubule networks at the plasma membrane.
Topics: Antiviral Agents; Cell Line; Cytomegalovirus; Herpesvirus 1, Human; Humans; Podophyllotoxin; RNA Viruses; Tubulin Modulators; Virus Internalization
PubMed: 27783035
DOI: 10.3390/v8100295 -
Blood Mar 2024
Topics: Humans; Gold; Etoposide; Lymphohistiocytosis, Hemophagocytic
PubMed: 38451514
DOI: 10.1182/blood.2023023123 -
Molecules (Basel, Switzerland) Jan 2020Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is... (Review)
Review
Lignans are widely produced by various plant species; they are a class of natural products that share structural similarity. They usually contain a core scaffold that is formed by two or more phenylpropanoid units. Lignans possess diverse pharmacological properties, including their antiviral activities that have been reported in recent years. This review discusses the distribution of lignans in nature according to their structural classification, and it provides a comprehensive summary of their antiviral activities. Among them, two types of antiviral lignans-podophyllotoxin and bicyclol, which are used to treat venereal warts and chronic hepatitis B (CHB) in clinical, serve as examples of using lignans for antivirals-are discussed in some detail. Prospects of lignans in antiviral drug discovery are also discussed.
Topics: Antiviral Agents; Benzodioxoles; Biological Products; Biphenyl Compounds; Drug Development; Furans; Lignans; Masoprocol; Plants; Podophyllotoxin
PubMed: 31906391
DOI: 10.3390/molecules25010183 -
International Journal of Molecular... Jun 2021Polyphenols are naturally occurring compounds found in abundance in fruits and vegetables. Their health-promoting properties and their use in the prevention and... (Review)
Review
Polyphenols are naturally occurring compounds found in abundance in fruits and vegetables. Their health-promoting properties and their use in the prevention and treatment of many human diseases, including cancer, have been known for years. Many anti-cancer drugs are derived from these natural compounds. Etoposide, which is a semi-synthetic derivative of podophyllotoxin, a non-alkaloid lignan isolated from the dried roots and rhizomes of or (Berberidaceae), is an example of such a compound. In this review, we present data on the effects of polyphenols on the anti-cancer activity of etoposide in in vitro and in vivo studies.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biomarkers; Cell Line, Tumor; Cell Proliferation; Cell Survival; Disease Models, Animal; Drug Synergism; Etoposide; Humans; Neoplasms; Polyphenols; Structure-Activity Relationship; Topoisomerase II Inhibitors; Xenograft Model Antitumor Assays
PubMed: 34202987
DOI: 10.3390/ijms22126602 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2021Podophyllotoxin (PTOX) is an aryl-tetralin lignan of plant origin found in some species of Podophyllum such as Dysosma versipellis, Diphylleia sinensis, and... (Review)
Review
Podophyllotoxin (PTOX) is an aryl-tetralin lignan of plant origin found in some species of Podophyllum such as Dysosma versipellis, Diphylleia sinensis, and Sinopodophyllum hexandrum. Etoposide and teniposide are produced semisynthetically from PTOX and used clinically to treat several forms of cancer. As a typical representative of new drug discovery from natural products, the production of PTOX solely depends on extraction from plants, resulting in severe contradiction between supply and demand. With the advantages of unconstrained resources and eco-friendly reaction conditions, biosynthesis method has become a trend in the production of PTOX and its derivatives. In this review, we summarize the research progress of PTOX biosynthesis in plants and expound the functions of the key enzymes as well as their subcellular location. The synthetic biology for production of PTOX intermediates in a tobacco chassis is also introduced. Finally, the heterologous expression and biotransformation of PTOX in microorganisms is summarized, which sets the foundation for the efficient microbial production of PTOX using cell factories.
Topics: Genes, Plant; Podophyllotoxin; Podophyllum
PubMed: 34227292
DOI: 10.13345/j.cjb.210258