Search results for "Antimalarial"
showing 10 items of 58 documents
Toxicity of the antimalarial artemisinin and its dervatives.
2010
As long as no effective malaria vaccine is available, chemotherapy belongs to the most important weapons fighting malaria. One of the most promising new drug developments is the sesquiterpene artemisinin (ARS) and its derivatives, e.g., artemether, arteether, and sodium artesunate. Large clinical studies and meta-analyses did not show serious side effects, although proper monitoring of adverse effects in developing countries might not be a trivial task. There is a paucity of large-scale clinical trials suitable to detect rare but significant toxicity. Therefore, a final and definitive statement on the safety of artemisinins still cannot be made. In contrast, animal experiments show consider…
Cutaneous Lupus Erythematosus
2008
Lupus erythematosus (LE) is an inflammatory autoimmune disease, characterized by a heterogeneous clinical presentation. The skin lesions are one of the most frequent symptoms of the disease and present with a broad spectrum of LE-nonspecific and LE-specific cutaneous manifestations. Therefore, the development of a classification for skin lesions in the disease has proven difficult. For example, the LE-nonspecific cutaneous manifestations include livedo racemosa, thrombophlebitis, and leukocytoclastic vasculitis and can be associated with high disease activity and systemic organ involvement. The LE-specific cutaneous manifestations encompass the subtypes of cutaneous lupus erythematosus (CLE…
Artesunate Activates Mitochondrial Apoptosis in Breast Cancer Cells via Iron-catalyzed Lysosomal Reactive Oxygen Species Production
2011
The antimalarial agent artesunate (ART) activates programmed cell death (PCD) in cancer cells in a manner dependent on the presence of iron and the generation of reactive oxygen species. In malaria parasites, ART cytotoxicity originates from interactions with heme-derived iron within the food vacuole. The analogous digestive compartment of mammalian cells, the lysosome, similarly contains high levels of redox-active iron and in response to specific stimuli can initiate mitochondrial apoptosis. We thus investigated the role of lysosomes in ART-induced PCD and determined that in MCF-7 breast cancer cells ART activates lysosome-dependent mitochondrial outer membrane permeabilization. ART impac…
Factors determining sensitivity or resistance of tumor cell lines towards artesunate.
2009
Clinical oncology is still challenged by the development of drug resistance of tumors that result in poor prognosis for patients. There is an urgent necessity to understand the molecular mechanisms of resistance and to develop novel therapy strategies. Artesunate (ART) is an anti-malarial drug, which also exerts profound cytotoxic activity towards cancer cells. We first applied a gene-hunting approach using cluster and COMPARE analyses of microarray-based transcriptome-wide mRNA expression profiles. Among the genes identified by this approach were genes from diverse functional groups such as structural constituents of ribosomes (RPL6, RPL7, RPS12, RPS15A), kinases (CABC1, CCT2, RPL41), tran…
Solid-State Electrochemical Assay of Heme-Binding Molecules for Screening of Drugs with Antimalarial Potential
2013
The interaction between heme and ligands is the basis for a variety of tests aimed at the discovery of antiplasmodial molecules. Two electrochemical methods for the screening of molecules with potential antimalarial activity through heme-binding mechanism are described. The first method is applicable to lipophilic environment, by using solution phase electrochemistry in DMSO solutions of Fe(III)-heme plus the tested compounds at carbon electrodes. This method provides well-defined voltammetric signals, characteristic of the heme-ligand (L) interaction. The second method involves aqueous media at biological pH and the use of voltammetry of immobilized particles, by means of microparticulate …
Chloroquine for COVID-19: rationale, facts, hopes
2020
The tragedy of the pandemic coronavirus disease 2019 (COVID-19) led to a desperate search for effective treatments. Chloroquine (CQ), an aminoquinoline used for many years for the prophylaxis and therapy of malaria and autoimmune diseases, has been put forward as a treatment option. The fact that CQ is not patented and has been in clinical use for years is a major advantage. CQ has been shown to have antiviral effects in SARS, MERS, Ebola, and HIV infections, but without data showing clinical effectiveness [1, 2]. Does the current level of evidence suffice for prescribing CQ for COVID-19?
Polyoxygenated Cyclohexenes and Other Constituents of Cleistochlamys kirkii Leaves.
2016
Thirteen new metabolites, including the polyoxygenated cyclohexene derivatives cleistodiendiol (1), cleistodienol B (3), cleistenechlorohydrins A (4) and B (5), cleistenediols A-F (6-11), cleistenonal (12), and the butenolide cleistanolate (13), 2,5-dihydroxybenzyl benzoate (cleistophenolide, 14), and eight known compounds (2, 15-21) were isolated from a MeOH extract of the leaves of Cleistochlamys kirkii. The purified metabolites were identified by NMR spectroscopic and mass spectrometric analyses, whereas the absolute configurations of compounds 1, 17, and 19 were established by single-crystal X-ray diffraction. The configuration of the exocyclic double bond of compound 2 was revised base…
Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium
2013
Current malaria therapeutics demands strategies able to selectively deliver drugs to Plasmodium-infected red blood cells (pRBCs) in order to limit the appearance of parasite resistance. Here, the poly(amidoamines) AGMA1 and ISA23 have been explored for the delivery of antimalarial drugs to pRBCs. AGMA1 has antimalarial activity per se as shown by its inhibition of the in vitro growth of Plasmodium falciparum, with an IC50 of 13.7 μM. Fluorescence-assisted cell sorting data and confocal fluorescence microscopy and transmission electron microscopy images indicate that both polymers exhibit preferential binding to and internalization into pRBCs versus RBCs, and subcellular targeting to the par…
Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Proguanil Hydrochloride
2018
Abstract Literature data relevant to the decision to waive in vivo bioequivalence testing for the approval of generic immediate release solid oral dosage forms of proguanil hydrochloride are reviewed. To elucidate the Biopharmaceutics Classification System (BCS) classification, experimental solubility and dissolution studies were also carried out. The antimalarial proguanil hydrochloride, effective via the parent compound proguanil and the metabolite cycloguanil, is not considered to be a narrow therapeutic index drug. Proguanil hydrochloride salt was shown to be highly soluble according to the U.S. Food and Drug Administration, World Health Organization, and European Medicines Agency guide…
Molecular interaction of artemisinin with translationally controlled tumor protein (TCTP) of Plasmodium falciparum
2012
Malaria causes millions of death cases per year. Since Plasmodium falciparum rapidly develops drug resistance, it is of high importance to investigate potential drug targets which may lead to novel rational therapy approaches. Here we report on the interaction of translationally controlled tumor protein of P. falciparum (PfTCTP) with the anti-malarial drug artemisinin. Furthermore, we investigated the crystal structure of PfTCTP. Using mass spectrometry, bioinformatic approaches and surface plasmon resonance spectroscopy, we identified novel binding sites of artemisinin which are in direct neighborhood to amino acids 19-46, 108-134 and 140-163. The regions covered by these residues are know…