Alkaloids Induce Programmed Cell Death in Bloodstream Forms of Trypanosomes (Trypanosoma b. brucei)

The potential induction of a programmed cell death (PCD) in Trypanosoma b. brucei by 55 alkaloids of the quinoline, quinolizidine, isoquinoline, indole, terpene, tropane, steroid, and piperidine type was studied by measuring DNA fragmentation and changes in mitochondrial membrane potential. For comparison, the induction of apoptosis by the same alkaloids in human leukemia cells (Jurkat APO-S) was tested. Several alkaloids of the isoquinoline, quinoline, indole and steroidal type (berberine, chelerythrine, emetine, sanguinarine, quinine, ajmalicine, ergotamine, harmine, vinblastine, vincristine, colchicine, chaconine, demissidine and veratridine) induced programmed cell death, whereas quinolizidine, tropane, terpene and piperidine alkaloids were mostly inactive. Effective PCD induction (EC50 below 10 µM) was caused in T. brucei by chelerythrine, emetine, sanguinarine, and chaconine. The active alkaloids can be characterized by their general property to inhibit protein biosynthesis, to intercalate DNA, to disturb membrane fluidity or to inhibit microtubule formation.

• Publication year

  2008

• Venue

  Molecules

• Publication date

  2008-10-01

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.3390/molecules13102462PMID 18833031PMCID 6244846
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• The toxic effects of piperine against Trypanosoma cruzi: ultrastructural alterations and reversible blockage of cytokinesis in epimastigote forms

  2008cited by this paper
• Chapter 1 Allelochemical Properties or the Raison D'être of Alkaloids

  2008cited by this paper
• Induction of Apoptosis by Alkaloids, Non-Protein Amino Acids, and Cardiac Glycosides in Human Promyelotic HL-60 Cells

  2007cited by this paper
• Molecular modes of action of cytotoxic alkaloids: from DNA intercalation, spindle poisoning, topoisomerase inhibition to apoptosis and multiple drug resistance.

  2007influential reference
• Efficacy and mechanisms of alpha-solasonine-and alpha-solamargine-induced cytolysis on two strains of Trypanosoma cruzi.

  2006cited by this paper
• Efficacy and Mechanisms of α-Solasonine-and α-Solamargine-Induced Cytolysis on Two Strains of Trypanosoma cruzi

  2006cited by this paper
• Control mechanisms of tubulin gene expression in Trypanosoma cruzi.

  2006cited by this paper
• Discovery of Trypanocidal Compounds by Whole Cell HTS of Trypanosoma brucei

  2006cited by this paper
• Prostaglandin-induced programmed cell death in Trypanosoma brucei involves oxidative stress

  2006cited by this paper
• Death of a trypanosome: a selfish altruism.

  2006cited by this paper
• Caspase-independent cell death

  2005cited by this paper
• Bioactive cinchona alkaloids from Remijia peruviana.

  2005cited by this paper
• Prostaglandin D2 induces programmed cell death in Trypanosoma brucei bloodstream form

  2005cited by this paper
• Toxic effects of natural piperine and its derivatives on epimastigotes and amastigotes of Trypanosoma cruzi.

  2004cited by this paper
• Trypanocidal constituents in plants 3. Leaves of Garcinia intermedia and heartwood of Calophyllum brasiliense.

  2004cited by this paper
• Caspase-independent cell death?

  2004cited by this paper
• Mitochondrial effectors in caspase‐independent cell death

  2004cited by this paper
• Caspase-independent cell death in T lymphocytes

  2003cited by this paper
• Natural Products as potential antiparasitic drugs.

  2002cited by this paper
• In Vitro Effect of Alkaloids on Bloodstream Forms of Trypanosoma brucei and T. congolense

  2001influential reference
• The mitochondrion in apoptosis: how Pandora's box opens

  2001cited by this paper
• In vitro effect of alkaloids on bloodstream forms of Trypanosoma brucei and T. congolense.

  2001cited by this paper
• Interference of alkaloids with neuroreceptors and ion channels

  2000cited by this paper
• Effects of some beta-carboline alkaloids on intact Trypanosoma cruzi epimastigotes.

  1999cited by this paper
• CD95(APO-1/Fas)-mediated apoptosis: live and let die.

  1999cited by this paper
• MEASURING THE COSTS OF AFRICAN ANIMAL TRYPANOSOMOSIS, THE POTENTIAL BENEFITS OF CONTROL AND RETURNS TO RESEARCH

  1999cited by this paper
• Modes of Action of Allelochemical Alkaloids: Interaction with Neuroreceptors, DNA, and Other Molecular Targets

  1998cited by this paper
• Inhibition of Trypanosoma cruzi Growth in vitro by Solanum Alkaloids: A Comparison with Ketoconazole

  1998cited by this paper
• Alkaloids: biochemistry, ecology, and medicinal applications.

  1998cited by this paper
• Drug resistance in trypanosomatids.

  1997cited by this paper
• The current status of antiparasite chemotherapy

  1997cited by this paper
• Current public health status of the trypanosomiases and leishmaniases.

  1997cited by this paper
• Apoptosis in procyclic Trypanosoma brucei rhodesiense in vitro.

  1996cited by this paper
• Apoptosis in a unicellular eukaryote (Trypanosoma cruzi): implications for the evolutionary origin and role of programmed cell death in the control of cell proliferation, differentiation and survival.

  1995cited by this paper
• A rapid and simple method for measuring thymocyte apoptosis by propidium iodide staining and flow cytometry.

  1991cited by this paper
• Plant-derived alkaloids active against Trypanosoma cruzi.

  1987cited by this paper
• Cultivation in a semi‐defined medium of animal infective forms of Trypanosoma brucei, T. equiperdum, T. evansi, T. rhodesiense and T. gambiense.

  1985cited by this paper
• The influence of hydroxyurea and colchicine on growth and morphology of Trypanosoma cruzi.

  1978cited by this paper
• In vitro antitrypanosomal activity of certain alkaloids against Trypanosoma lewisi.

  1976cited by this paper
• In vitro antitrypanosomal activity of certain alkaloids against Trypanosoma lewisi.

  1976cited by this paper
• [Trypanocidal activity of some ellipticine derivatives against Trypanosoma cruzi cultured in vitro].

  1975cited by this paper
• Apoptosis: A Basic Biological Phenomenon with Wide-ranging Implications in Tissue Kinetics

  1972cited by this paper
• EMETINE AND SOME RELATED COMPOUNDS IN EXPERIMENTAL CHAGAS' DISEASE.

  1964cited by this paper
• EMETINE AND SOME RELATED COMPOUNDS IN EXPERIMENTAL CHAGAS' DISEASE.

  1964cited by this paper

• Trypanocidal Potentials of Jatropha curcas L. 1753 Leaf Extracts and Fractions in vivo

  2025cites this paper
• Research Approaches for the Discovery of Trypanocidal Molecular Prototypes from Plants

  2025cites this paper
• Cinchonine Downregulates the Cyclooxygenase‐2 Expression of Leukemic Cells and Suppresses Proliferation by Inducing the G0/G1 Phase Arrest

  2025influential citation
• Alkaloids from the genus Vinca L. (Apocynaceae): a comprehensive biological and structural review

  2025cites this paper
• Extracts of the cyanobacteria Microcystis flos-aquae contain potent anti-Trypanosoma compounds

  2024cites this paper
• Sanguinarine as an Antiparasitic against Helminths and Protozoa with Importance in Human and Veterinary Medicine: A Systematic Review

  2023cites this paper
• Cinchonine: A Versatile Pharmacological Agent Derived from Natural Cinchona Alkaloids.

  2023cites this paper
• Intracellular ROS production and apoptotic effect of Quinoline and Isoquinoline alkaloids on the growth of Trypanosoma evansi.

  2023cites this paper
• In vitro and in vivo evaluation of efficacy of berberine chloride: phyto-alternative approach against Trypanosoma evansi infection.

  2023cites this paper
• ANTIBACTERIAL ACTIVITY OF ALKALOIDS EXTRACT FROM PEGANUM HARMALA L. SEEDS AGAINST STAPHYLOCOCCUS AUREUS AND KLEBSILLA PNEUMONIA ISOLATED FROM BURNS.

  2021cites this paper
• Multiple Molecular Mechanisms to Overcome Multidrug Resistance in Cancer by Natural Secondary Metabolites

  2021cites this paper
• Identification of clinically approved small molecules that inhibit growth and affect transcript levels of developmentally regulated genes in the African trypanosome

  2020cites this paper
• Venom alkaloids against Chagas disease parasite: search for effective therapies

  2020cites this paper
• Title: New Approaches with Natural Product Drugs for Overcoming Multidrug Resistance in Cancer Short running title: Natural Products and Cancer MDR

  2020cites this paper
• Nanotechnology enabled the enhancement of antitrypanosomal activity of piperine against Trypanosoma evansi.

  2020cites this paper
• Synthesis of conjugates of (−)-cytisine derivatives with ferrocene-1-carbaldehyde and their cytotoxicity against HEK293, Jurkat, A549, MCF-7 and SH-SY5Y cells

  2020cites this paper
• Analysis of alkaloids (indole alkaloids, isoquinoline alkaloids, tropane alkaloids)

  2020cites this paper
• A Paradoxically Significant Medicinal Plant Carapichea ipecacuanha: A Review

  2020cites this paper
• Encapsulation of cinnamic acid and galangal extracts in coconut (Cocos nucifera L.) liposomes

  2020cites this paper
• (+)-Spectaline and Iso-6-Spectaline Induce a Possible Cross-Talk between Autophagy and Apoptosis in Trypanosoma brucei rhodesiense

  2019cites this paper
• Rh-Catalyzed tandem C-C/C-N bond formation of quinoxalines with alkynes leading to heterocyclic ammonium salts.

  2019cites this paper
• Cell death pathways in pathogenic trypanosomatids: lessons of (over)kill

  2019cites this paper
• Identification of clinically approved small molecules that inhibit growth and promote surface remodeling in the African trypanosome

  2019cites this paper
• Design, synthesis and apoptosis-related antiproliferative activities of chelidonine derivatives.

  2019cites this paper
• Emetine exhibits anticancer activity in breast cancer cells as an antagonist of Wnt/β-catenin signaling

  2019cites this paper
• Promising trypanocidal heterocyclic compounds of natural origin and their synthetic analogs

  2019cites this paper
• In vitro antiprotozoal activity of some medicinal plants against sleeping sickness, Chagas disease and leishmaniasis.

  2018cites this paper
• Atropine exposure in adolescence predispose to adult memory loss in Wistar rats

  2018cites this paper
• Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae

  2018cites this paper
• Context-dependent medicinal effects of anabasine and infection-dependent toxicity in bumble bees

  2017cites this paper
• In vitro antitrypanosomal potential of chloroform leaf extract of Punica granatum L. on Trypanosoma brucei brucei and Trypanosoma evansi

  2017cites this paper
• Identification of breast cancer hub genes and analysis of prognostic values using integrated bioinformatics analysis

  2017cites this paper
• Screening a Natural Product-Based Library against Kinetoplastid Parasites

  2017cites this paper
• Effects of Thai piperaceae plant extracts on Neospora caninum infection.

  2017cites this paper
• Expanding the therapeutic spectrum of artemisinin: Activity against infectious diseases beyond malaria and novel pharmaceutical developments

  2016cites this paper
• High‐Valent Pentamethylcyclopentadienylcobalt(III) or ‐iridium(III)‐Catalyzed CH Annulation with Alkynes: Synthesis of Heterocyclic Quaternary Ammonium Salts

  2016cites this paper
• Synthesis and antitumor activity of novel N-substituted tetrahydro-β-carboline-imidazolium salt derivatives.

  2016cites this paper
• How do the alkaloids emetine and homoharringtonine kill trypanosomes? An insight into their molecular modes of action.

  2016cites this paper
• Investigating ethnopharmacology-based natural product leads for antimalarial drug discovery

  2016cites this paper
• Efficacy and Mechanism of Action of Low Dose Emetine against Human Cytomegalovirus

  2016cites this paper
• Sanguinaria canadensis: Traditional Medicine, Phytochemical Composition, Biological Activities and Current Uses

  2016cites this paper
• A Review of Bioinsecticidal Activity of Solanaceae Alkaloids

  2016cites this paper
• Between Armour and Weapons — Cell Death Mechanisms in Trypanosomatid Parasites

  2015cites this paper
• Colchicine treatment reversibly blocks cytokinesis but not mitosis in Trypanosoma cruzi epimastigotes

  2015influential citation
• Secondary metabolites in floral nectar reduce parasite infections in bumblebees

  2015cites this paper
• Modes of Action of Herbal Medicines and Plant Secondary Metabolites

  2015cites this paper
• Membrane Interactions of Phytochemicals as Their Molecular Mechanism Applicable to the Discovery of Drug Leads from Plants

  2015cites this paper
• Emetine inhibits migration and invasion of human non-small-cell lung cancer cells via regulation of ERK and p38 signaling pathways.

  2015cites this paper
• New Approaches With Natural Product Drugs for Overcoming Multidrug Resistance in Cancer.

  2015cites this paper
• Combinations of Alkaloids Affecting Different Molecular Targets with the Saponin Digitonin Can Synergistically Enhance Trypanocidal Activity against Trypanosoma brucei brucei

  2015cites this paper
• Natural Products Modulate the Multifactorial Multidrug Resistance of Cancer

  2015cites this paper
• Invivo Anti-Trypanosomal Activity of the Leaf Extracts of Albizia Schimperiana (Fabaceae) Against Trypanosoma Congolense Infection in Mice

  2015cites this paper
• The alkaloid emetine sensitizes ovarian carcinoma cells to cisplatin through downregulation of bcl-xL.

  2015cites this paper
• Isolation and Structural Elucidation of Bioactive Compounds from Bangladeshi Medicinal Plants with a Focus on Novel Anticancer Compounds

  2014cites this paper
• Holarrhena floribunda leaves as a potential source of bioactive anticancer compounds

  2014cites this paper
• Chemical Composition and Biological Activity of Essential Oils of Cumin and Coriander Fruits from Egypt

  2014cites this paper
• Xanthium strumarium L. Extracts Produce DNA Damage Mediated by Cytotoxicity in In Vitro Assays but Does Not Induce Micronucleus in Mice

  2014cites this paper
• Synthesis, antileishmanial and antitrypanosomal activities of N-substituted tetrahydro-β-carbolines.

  2014cites this paper
• Nep1-like protein from Moniliophthora perniciosa induces a rapid proteome and metabolome reprogramming in cells of Nicotiana benthamiana.

  2014cites this paper
• Emetine enhances the tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis of pancreatic cancer cells by downregulation of myeloid cell leukemia sequence-1 protein.

  2014cites this paper
• Evaluation of in vivo antitrypanosomal activity of crude extracts of Artemisia abyssinica against aTrypanosoma congolense isolate

  2014cites this paper
• In Vitro Effect of Aqueous Extract and Fraction IV Portion of Ximenia americana Stem Bark on Trypanosoma congolense DNA

  2014cites this paper
• Evaluation of the In Vitro Efficacy of Artemisia annua, Rumex abyssinicus, and Catha edulis Forsk Extracts in Cancer and Trypanosoma brucei Cells

  2013cites this paper
• Sesquiterpenes and Cytotoxicity

  2013cites this paper
• Chemical composition of celandine (Chelidonium majus L.) extract and its effects on Botrytis tulipae (Lib.) Lind fungus and the tulip.

  2013cites this paper
• Modulation of multidrug resistance in cancer cells by chelidonine and Chelidonium majus alkaloids.

  2013cites this paper
• Gold(III) complexes of pyridyl- and isoquinolylamido ligands: structural, spectroscopic, and biological studies of a new class of dual topoisomerase I and II inhibitors.

  2013cites this paper
• Evolutionary cell biology of chromosome segregation: insights from trypanosomes

  2013cites this paper
• Synergism of three-drug combinations of sanguinarine and other plant secondary metabolites with digitonin and doxorubicin in multi-drug resistant cancer cells.

  2012cites this paper
• Medicinal Plants: A Source of Anti-Parasitic Secondary Metabolites

  2012cites this paper
• A review on medicinal importance, pharmacological activity and bioanalytical aspects of beta-carboline alkaloid ''Harmine''.

  2012cites this paper
• The potential of secondary metabolites from plants as drugs or leads against protozoan neglected diseases - part II.

  2012cites this paper
• Diversity of Pharmacological Properties in Chinese and European Medicinal Plants: Cytotoxicity, Antiviral and Antitrypanosomal Screening of 82 Herbal Drugs

  2011cites this paper
• The Growth Suppressing Effects of Girinimbine on Hepg2 Involve Induction of Apoptosis and Cell Cycle Arrest

  2011cites this paper
• Potent antiprotozoal activity of a novel semi-synthetic berberine derivative.

  2011cites this paper
• Biological Activities of Emetine

  2011cites this paper
• Biological Activities of Xanthatin from Xanthium strumarium Leaves

  2011influential citation
• Chemical-Biology of Natural Products from Medicinal Plants for Cancer Therapy

  2010cites this paper
• Targeting essential pathways in trypanosomatids gives insights into protozoan mechanisms of cell death

  2010cites this paper
• In Vitro activities of plant extracts from Saudi Arabia against malaria, leishmaniasis, sleeping sickness and Chagas disease

  2010cites this paper
• Molecular Modes of Action of Defensive Secondary Metabolites

  2010cites this paper
• Chemical composition and biological activity of the essential oil obtained from Bupleurum marginatum (Apiaceae).

  2009cites this paper
• Limited uptake of the cyanobacterial toxin cylindrospermopsin by Vero cells.

  2009cites this paper
• CELL SUICIDE OR PROGRAMMED CELL DEATH

  2009cites this paper
• Chemical composition and biological activity of the essential oil obtained from Bupleurum marginatum (Apiaceae)

  2009cites this paper
• In-vitro and in-vivo Anticoccidial Activities of Berberine against Murine Eimeria papillata Infection

  year unknowncites this paper