525 results match your criteria prenylation inhibited

New Approaches to the Prevention and Treatment of Viral Diseases.

Arch Immunol Ther Exp (Warsz) 2021 Apr 3;69(1):10. Epub 2021 Apr 3.

N.F. Gamaleya National Research Center of Epidemiology and Microbiology of the Ministry of Health of Russia, Gamaleya 18, Moscow, Russia, 123098.

The review discusses a new approach to the prevention and treatment of viral infections based on the use of pine needles polyprenyl phosphate (PPP) and associated with the infringement of prenylation process-the attachment of farnesol or geranyl geraniol to the viral protein. Currently, prenylation has been detected in type 1 adenovirus, hepatitis C virus, several herpes viruses, influenza virus, HIV. However, this list is far from complete, given that prenylated proteins play an extremely important role in the activity of the virus. Read More

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Fluvastatin protects neuronal cells from hydrogen peroxide-induced toxicity with decreasing oxidative damage and increasing PI3K/Akt/mTOR signalling.

J Pharm Pharmacol 2021 Mar;73(4):515-521

Department of Gastroenterology, Hunan Provincial People's Hospital, The First-affiliated Hospital of Hunan Normal University, Changsha, People's Republic of China.

Background: Statins, the most effective lipoprotein-cholesterol lowering drugs, are widely used for patients with cardiovascular disease. The pleiotropic effects of statins have been recently gained attention for their both beneficial and deleterious effects on neurons. We investigated the effects and molecular mechanisms of fluvastatin at clinically relevant concentrations on neuronal cells after induction of oxidative stress. Read More

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Leptin activates Akt in oesophageal cancer cells via multiple atorvastatin-sensitive small GTPases.

Mol Cell Biochem 2021 Jun 13;476(6):2307-2316. Epub 2021 Feb 13.

Gastrioenterology Research Unit, Norwich Medical School, University of East Anglia, Norwich, NR4 7TJ, UK.

Obesity is a risk factor for Barrett's oesophagus and oesophageal adenocarcinoma. Adipose tissue secretes the hormone leptin. Leptin is a growth factor for several cell types, including Barrett's cells and oesophageal adenocarcinoma cells. Read More

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Benzoic acid inhibits Coenzyme Q biosynthesis in Schizosaccharomyces pombe.

PLoS One 2020 24;15(11):e0242616. Epub 2020 Nov 24.

Department of Life Sciences, Faculty of Life and Environmental Sciences, Shimane University, Matsue, Japan.

Coenzyme Q (CoQ, ubiquinone) is an essential component of the electron transport system in aerobic organisms. Human type CoQ10, which has 10 units of isoprene in its quinone structure, is especially valuable as a food supplement. Therefore, studying the biosynthesis of CoQ10 is important not only for increasing metabolic knowledge, but also for improving biotechnological production. Read More

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January 2021

Effect of simvastatin on cell proliferation and Ras activation in canine tumour cells.

Vet Comp Oncol 2021 Mar 24;19(1):99-108. Epub 2020 Aug 24.

Laboratory of Veterinary Internal Medicine, The United Graduate School of Veterinary Science, Yamaguchi University, Yamaguchi, Japan.

Statins are inhibitors of the mevalonate cascade that is responsible for cholesterol biosynthesis and the formation of intermediate metabolites, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) used in the prenylation of proteins. Although statins are widely used in the treatment of hypercholesterolemia, recent studies suggest that they also inhibit proliferation of tumour cells by reducing prenylation of small GTP-binding proteins, such as, Ras. This study aimed to evaluate the effect of simvastatin on cell proliferation and Ras activation in various canine tumour cell lines, including hemangiosarcoma (HSA), melanoma, and lymphoma cell lines. Read More

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Therapeutic potential of prenylated stilbenoid macasiamenene F through its anti-inflammatory and cytoprotective effects on LPS-challenged monocytes and microglia.

J Ethnopharmacol 2020 Dec 28;263:113147. Epub 2020 Jul 28.

Université Côte D'Azur, CNRS, IPMC, UMR7275, 660 Route des Lucioles, Sophia Antipolis, F-06560, Valbonne, France. Electronic address:

Ethnopharmacological Relevance: Macaranga Thou. (Euphorbiaceae) is a large genus that comprises over 300 species distributed between Western Africa and the islands of the South Pacific. Plants of this genus have a long-standing history of use in traditional medicine for different purposes, including the treatment of inflammation. Read More

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December 2020

Tipifarnib as a Precision Therapy for -Mutant Head and Neck Squamous Cell Carcinomas.

Mol Cancer Ther 2020 09 29;19(9):1784-1796. Epub 2020 Jul 29.

Kura Oncology, Inc., San Diego, California.

Tipifarnib is a potent and highly selective inhibitor of farnesyltransferase (FTase). FTase catalyzes the posttranslational attachment of farnesyl groups to signaling proteins that are required for localization to cell membranes. Although all RAS isoforms are FTase substrates, only HRAS is exclusively dependent upon farnesylation, raising the possibility that HRAS-mutant tumors might be susceptible to tipifarnib-mediated inhibition of FTase. Read More

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September 2020

Xanthine Oxidase Inhibition and Anti-LDL Oxidation by Prenylated Isoflavones from Root.

Molecules 2020 Jul 6;25(13). Epub 2020 Jul 6.

Division of Applied Life Science (BK21 Plus), IALS, Gyeongsang National University, Jinju 52828, Korea.

Xanthine oxidase is a frontier enzyme to produce oxidants, which leads to inflammation in the blood. Prenylated isoflavones from were found to display potent inhibition against xanthine oxidase (XO). All isolates (-) inhibited XO enzyme with IC ranging 7. Read More

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Mesenchymal subtype neuroblastomas are addicted to TGF-βR2/HMGCR-driven protein geranylgeranylation.

Sci Rep 2020 07 1;10(1):10748. Epub 2020 Jul 1.

Department of Biological Sciences, Columbia University, New York City, NY, 10027, USA.

The identification of targeted agents with high therapeutic index is a major challenge for cancer drug discovery. We found that screening chemical libraries across neuroblastoma (NBL) tumor subtypes for selectively-lethal compounds revealed metabolic dependencies that defined each subtype. Bioactive compounds were screened across cell models of mesenchymal (MESN) and MYCN-amplified (MYCNA) NBL subtypes, which revealed the mevalonate and folate biosynthetic pathways as MESN-selective dependencies. Read More

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Zoledronic acid inhibits the growth of leukemic MLL-AF9 transformed hematopoietic cells.

Heliyon 2020 Jun 5;6(6):e04020. Epub 2020 Jun 5.

Laboratory of Molecular Haematopoiesis and Stem Cell Biology, Dept. of Experimental and Clinical Medicine, University Magna Græcia, 88100 Catanzaro, Italy.

A leukemic model produced by transducing Cord Blood derived-hematopoietic CD34 cells with the MLL-AF9 translocation resulting in the oncogenic fusion protein, is used to assess for sensitivity to Zoledronic acid. These cells are practically immortalized and are of myeloid origin. Proliferation, clonogenic and stromal co-culture assays showed that the MLL-AF9 cells were considerably more sensitive to Zoledronic acid than normal hematopoietic CD34 cells or MS-5 stromal cells. Read More

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[vestigation of molecular factors determining BRAF-inhibitor sensitivity in solid tumors].

Eszter Molnár

Magy Onkol 2020 Mar 27;64(1):76-78. Epub 2019 Oct 27.

Patológiai Tudományok Doktori Iskola, Semmelweis Egyetem, Budapest, Hungary.

Targeted therapy for V600 BRAF mutant solid tumors already exists but resistance to the treatment is still a serious problem to be solved. Moreover, there are currently no approved targeted therapeutic options against non-V600 BRAF mutant tumors. Here we studied targeted therapy resistance mechanisms of V600 BRAF mutant melanoma and also explored potential alternative solutions for their treatment. Read More

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Cholesterol-lowering drug pitavastatin targets lung cancer and angiogenesis via suppressing prenylation-dependent Ras/Raf/MEK and PI3K/Akt/mTOR signaling.

Anticancer Drugs 2020 04;31(4):377-384

Department of Thoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China.

Therapeutic agents that target both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy, particularly in lung cancer due to the critical roles of angiogenesis during lung cancer progression and metastasis. In this work, we showed that pitavastatin, a novel cholesterol-lowering drug, potently inhibited lung cancer cells and angiogenesis. This was achieved by the induction of apoptosis and inhibition of proliferation of lung cancer cells and human lung tumor-associated endothelial cell. Read More

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Regulation of Small GTPase Prenylation in the Nervous System.

Mol Neurobiol 2020 May 27;57(5):2220-2231. Epub 2020 Jan 27.

Texas Woman's University, Denton, TX, USA.

Mevalonate pathway inhibitors have been extensively studied for their roles in cholesterol depletion and for inhibiting the prenylation and activation of various proteins. Inhibition of protein prenylation has potential therapeutic uses against neurological disorders, like neural cancers, neurodegeneration, and neurotramatic lesions. Protection against neurodegeneration and promotion of neuronal regeneration is regulated in large part by Ras superfamily small guanosine triphosphatases (GTPases), particularly the Ras, Rho, and Rab subfamilies. Read More

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[Impact of prenylation inhibition on RAS mutant tumors in preclinical studies].

Magy Onkol 2019 Dec 30;63(4):320-329. Epub 2019 Oct 30.

II. Sz. Patológiai Intézet, Semmelweis Egyetem, Budapest, Hungary.

Oncogenic mutation of RAS occurs in 20-25% of all malignancies. Our research group have examined inhibition of RAS prenylation on RAS wild type and RAS mutated melanoma, colorectal cancer and lung adenocarcinoma cell lines. Effects of clinically approved bisphosphonate (zoledronic acid) and its lipophilic derivate (BPH1222) on cell viability and cell signaling were determined. Read More

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December 2019

Farnesyl Pyrophosphate Synthase as a Target for Drug Development: Discovery of Natural-Product-Derived Inhibitors and Their Activity in Pancreatic Cancer Cells.

J Med Chem 2019 12 2;62(23):10867-10896. Epub 2019 Dec 2.

School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology , Tsinghua University , 100084 Beijing , China.

Human farnesyl pyrophosphate synthase ( FPPS, FPPS) is a target for treating bone resorption diseases and some cancers. FPPS is potently inhibited by bisphosphonates, but due to poor cell penetration and distribution in soft tissue, there is currently interest in the development of non-bisphosphonate inhibitors as cancer therapeutics. Here, we report the discovery and development of FPPS inhibitors based on the phenolic diterpene carnosic acid (), an antimicrobial found in rosemary and sage, which showed better cellular anticancer activities than the bisphosphonate drug zoledronate in pancreatic cancer cell lines, as well as an FPPS-dependent mechanism of action. Read More

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December 2019

Atorvastatin Targets the Islet Mevalonate Pathway to Dysregulate mTOR Signaling and Reduce β-Cell Functional Mass.

Diabetes 2020 01 24;69(1):48-59. Epub 2019 Oct 24.

Department of Metabolism and Endocrinology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China

Statins are cholesterol-lowering agents that increase the incidence of diabetes and impair glucose tolerance via their detrimental effects on nonhepatic tissues, such as pancreatic islets, but the underlying mechanism has not been determined. In atorvastatin (ator)-treated high-fat diet-fed mice, we found reduced pancreatic β-cell size and β-cell mass, fewer mature insulin granules, and reduced insulin secretion and glucose tolerance. Transcriptome profiling of primary pancreatic islets showed that ator inhibited the expression of pancreatic transcription factor, mechanistic target of rapamycin (mTOR) signaling, and small G protein (sGP) genes. Read More

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January 2020

The Antitumor Effect of Lipophilic Bisphosphonate BPH1222 in Melanoma Models: The Role of the PI3K/Akt Pathway and the Small G Protein Rheb.

Int J Mol Sci 2019 Oct 3;20(19). Epub 2019 Oct 3.

Department of Pathology, Semmelweis University, H-1091 Budapest, Hungary.

Malignant melanoma is one of the most metastatic cancer types, and despite recent success with novel treatment strategies, there is still a group of patients who do not respond to any therapies. Earlier, the prenylation inhibitor hydrophilic bisphosphonate zoledronic acid (ZA) was found to inhibit melanoma growth in vitro, but only a weaker effect was observed in vivo due to its hydrophilic properties. Recently, lipophilic bisphosphonates (such as BPH1222) were developed. Read More

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October 2019

Simvastatin increases temozolomide-induced cell death by targeting the fusion of autophagosomes and lysosomes.

FEBS J 2020 03 14;287(5):1005-1034. Epub 2019 Oct 14.

Department of Human Anatomy and Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada.

Temozolomide (TMZ) is a chemotherapy agent used to treat Grade IV astrocytoma, also known as glioblastoma (GBM). TMZ treatment causes DNA damage that results in tumor cell apoptosis and increases the survival rate of GBM patients. However, chemoresistance as a result of TMZ-induced autophagy significantly reduces this anticancer effects over time. Read More

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Loss of CENPF leads to developmental failure in mouse embryos.

Cell Cycle 2019 Oct 3;18(20):2784-2799. Epub 2019 Sep 3.

The Research Centre for Laboratory Animal Science, State Key Laboratory of Reproductive Regulation & Breeding of Grassland Livestock, School of Life Science, Inner Mongolia University , Hohhot , People's Republic of China.

Aneuploidy caused by abnormal chromosome segregation during early embryo development leads to embryonic death or congenital malformation. Centromere protein F (CENPF) is a member of centromere protein family that regulates chromosome segregation during mitosis. However, its necessity in early embryo development has not been fully investigated. Read More

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October 2019

ICMT contributes to hepatocellular carcinoma growth, survival, migration and chemoresistance via multiple oncogenic pathways.

Biochem Biophys Res Commun 2019 10 24;518(3):584-589. Epub 2019 Aug 24.

Department of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, China.

Isoprenylcysteine carboxylmethyltransferase (Icmt) which catalyzes the final step of prenylation of many oncoproteins, such as Ras. Despite studies on Icmt and its regulation in biological activities of various cancers, little is known on the expression, function and mechanisms of the impact of Icmt on hepatocellular carcinoma (HCC). We report here the findings that Icmt is critical for HCC growth, migration, survival and chemoresistance by multiple oncogenic pathways. Read More

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October 2019

HIV-Nef Protein Transfer to Endothelial Cells Requires Rac1 Activation and Leads to Endothelial Dysfunction Implications for Statin Treatment in HIV Patients.

Circ Res 2019 10 27;125(9):805-820. Epub 2019 Aug 27.

From the Indiana University School of Medicine, Indianapolis (S.C., S.K.G., X.C., B.F.M., T.M.C., J.K., A.G.O., M.C.).

Rationale: Even in antiretroviral therapy-treated patients, HIV continues to play a pathogenic role in cardiovascular diseases. A possible cofactor may be persistence of the early HIV response gene Nef, which we have demonstrated recently to persist in the lungs of HIV+ patients on antiretroviral therapy. Previously, we have reported that HIV strains with Nef, but not Nef-deleted HIV strains, cause endothelial proinflammatory activation and apoptosis. Read More

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October 2019

Mechanisms of simvastatin myotoxicity: The role of autophagy flux inhibition.

Eur J Pharmacol 2019 Nov 23;862:172616. Epub 2019 Aug 23.

Department of Human Anatomy & Cell Science, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB, Canada; Center for Comparative Respiratory Biology and Medicine, Davis, CA, USA; Children's Hospital Research Institute of Manitoba, Winnipeg, MB, Canada; Research Institute of Oncology and Hematology, Cancer Care Manitoba, University of Manitoba, Winnipeg, Canada; Autophagy Research Center, Health Policy Research Centre, Shiraz University of Medical Science, Shiraz, Iran. Electronic address:

Statins are some of the most widely used drugs worldwide, but one of their major side effects is myotoxicity. Using mouse myoblast (C2C12) and human alveolar rhabdomyosarcoma cell lines (RH30) in both 2-dimensional (2D) and 3-dimensional (3D) cell culture, we investigated the mechanisms of simvastatin's myotoxicity. We found that simvastatin significantly reduced cell viability in C2C12 cells compared to RH30 cells. Read More

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November 2019

Antibacterial and Inhibitory Activities against Nitric Oxide Production of Coumaronochromones and Prenylated Isoflavones from .

J Nat Prod 2019 08 12;82(8):2343-2348. Epub 2019 Aug 12.

Center of Chemical Innovation for Sustainability (CIS) , Mae Fah Luang University , Chiang Rai 57100 , Thailand.

A chemical investigation of leaf and root extracts of led to the isolation and structural elucidation of four new prenylated isoflavones, millexatins G-J (-), and three new coumaronochromones, millexatins K-M (-), along with 16 known compounds. The structures of the new compounds were determined on the basis of NMR and MS data. Compound is a rare isoflavone having a 2-hydroxyethyl moiety at C-8, whereas the structures of compounds - formally arise from a ring closure through HO-2' and C-2. Read More

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Inhibition of mutant Kras and p53-driven pancreatic carcinogenesis by atorvastatin: Mainly via targeting of the farnesylated DNAJA1 in chaperoning mutant p53.

Mol Carcinog 2019 11 9;58(11):2052-2064. Epub 2019 Aug 9.

Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.

Recent studies have indicated that using statins to inhibit the mevalonate pathway induces mutant p53 degradation by impairing the interaction of mutant p53 with DnaJ subfamily A member 1 (DNAJA1). However, the role of the C-terminus of DNAJA1 with a CAAX box for farnesylation in the binding, folding, and translocation of client proteins such as mutant p53 is not known. In the present study, we used a genetically engineered mouse model of pancreatic carcinoma and showed that atorvastatin significantly increased animal survival and inhibited pancreatic carcinogenesis. Read More

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November 2019

Antimicrobial and antibiofilm activities of prenylated flavanones from Macaranga tanarius.

Phytomedicine 2019 Oct 13;63:153033. Epub 2019 Jul 13.

School of Chemical Engineering, Yeungnam University, Gyeongsan 38541, Republic of Korea. Electronic address:

Background: The emergence of antibiotic resistant microorganisms presents a worldwide problem that requires novel antibiotic and non-antibiotic strategies, and biofilm formation is a mechanism of drug resistance utilized by diverse microorganisms. The majority of microorganisms live in biofilms that help their survival against starvation, antimicrobial agents, and immunological defense systems. Therefore, it is important novel compounds be identified that inhibit biofilm formation and cell survival without drug resistance. Read More

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October 2019

Electroporated recombinant proteins as tools for in vivo functional complementation, imaging and chemical biology.

Elife 2019 07 16;8. Epub 2019 Jul 16.

Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, Dortmund, Germany.

Delivery of native or chemically modified recombinant proteins into mammalian cells shows promise for functional investigations and various technological applications, but concerns that sub-cellular localization and functional integrity of delivered proteins may be affected remain high. Here, we surveyed batch electroporation as a delivery tool for single polypeptides and multi-subunit protein assemblies of the kinetochore, a spatially confined and well-studied subcellular structure. After electroporation into human cells, recombinant fluorescent Ndc80 and Mis12 multi-subunit complexes exhibited native localization, physically interacted with endogenous binding partners, and functionally complemented depleted endogenous counterparts to promote mitotic checkpoint signaling and chromosome segregation. Read More

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Functional Regulation of an Oxidative Stress Mediator, Rac1, in Diabetic Retinopathy.

Mol Neurobiol 2019 Dec 13;56(12):8643-8655. Epub 2019 Jul 13.

Department of Ophthalmology, Visual and Anatomical Sciences, Wayne State University, 4717 St. Antoine, Detroit, MI, 48201, USA.

Purpose: Early activation of cytosolic NADPH oxidase-2 (Nox2) in diabetes increases retinal ROS production, damaging their mitochondria. The assembly of Nox2 holoenzyme requires activation of a small molecular weight G protein Rac1. Rac1 activation is regulated by guanine exchange factors and guanine nucleotide-dissociation inhibitors, and post-translational modifications assist in its association with exchange factors and dissociation inhibitors. Read More

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December 2019

Antispasmodic Activity of Prenylated Phenolic Compounds from the Root Bark of .

Molecules 2019 Jul 8;24(13). Epub 2019 Jul 8.

Institute of Pharmacognosy, Interdisciplinary Excellence Center, University of Szeged, H-6720 Szeged, Hungary.

Black mulberry is a widely acknowledged ancient traditional medicine. Its extract and constituents have been reported to exert various bioactivities including antimicrobial, hypotensive, analgesic etc. effects. Read More

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The chaperone SmgGDS-607 has a dual role, both activating and inhibiting farnesylation of small GTPases.

J Biol Chem 2019 08 13;294(31):11793-11804. Epub 2019 Jun 13.

Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109

Ras family small GTPases undergo prenylation (such as farnesylation) for proper localization to the plasma membrane, where they can initiate oncogenic signaling pathways. Small GTP-binding protein GDP-dissociation stimulator (SmgGDS) proteins are chaperones that bind and traffic small GTPases, although their exact cellular function is unknown. Initially, SmgGDS proteins were classified as guanine nucleotide exchange factors, but recent findings suggest that SmgGDS proteins also regulate prenylation of small GTPases in a substrate-selective manner. Read More

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Prenylated xanthones from Metaxya rostrata suppress FoxM1 and induce active cell death by distinct mechanisms.

Phytomedicine 2019 Jul 2;60:152912. Epub 2019 Apr 2.

Medical University Vienna, Department of Medicine I, Institute of Cancer Research, Borschkegasse 8a, 1090 Vienna, Austria. Electronic address:

Background: Metaxya rostrata C.Presl (Metaxyaceae) is a tree fern widespread in Central and South America and the dried rhizome is used in ethnic medicine against intestinal ulcers or tumors. An activity-guided isolation resulted in two structurally related xanthones: 2-deprenyl-rheediaxanthone B (XB) and 2-deprenyl-7-hydroxy-rheediaxanthone B (OH-XB). Read More

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