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Artemisinin toxicity

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https://www.readbyqxmd.com/read/28722611/phase-2a-open-label-4-escalating-dose-randomized-multicenter-study-evaluating-the-safety-and-activity-of-ferroquine-ssr97193-plus-artesunate-versus-amodiaquine-plus-artesunate-in-african-adult-men-with-uncomplicated-plasmodium-falciparum-malaria
#1
Christian Supan, Ghyslain Mombo-Ngoma, Maryvonne Kombila, Carmen L Ospina Salazar, Jana Held, Bertrand Lell, Cathy Cantalloube, Elhadj Djeriou, Bernhards Ogutu, John Waitumbi, Nekoye Otsula, Duncan Apollo, Mark E Polhemus, Peter G Kremsner, Douglas S Walsh
Artemisinin-based combination therapies are recommended as first-line agents for treating uncomplicated Plasmodium falciparum malaria. Ferroquine, a 4-aminoquinolone, is a novel long-acting combination partner for fast-acting drugs like artesunate (AS). We did a small phase 2a, multicenter, open-label, safety-focused dose-ranging randomized study of ferroquine at three African hospitals: two Gabonese and one Kenyan. We recruited adult men with symptomatic uncomplicated P. falciparum monoinfection. Four escalating doses of ferroquine (100, 200, 400, and 600 mg) were assessed in sequence, versus an amodiaquine comparator...
May 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28686181/how-can-synergism-of-traditional-medicines-benefit-from-network-pharmacology
#2
REVIEW
Haidan Yuan, Qianqian Ma, Heying Cui, Guancheng Liu, Xiaoyan Zhao, Wei Li, Guangchun Piao
Many prescriptions of traditional medicines (TMs), whose efficacy has been tested in clinical practice, have great therapeutic value and represent an excellent resource for drug discovery. Research into single compounds of TMs, such as artemisinin from Artemisia annua L., has achieved great success; however, it has become evident that a TM prescription (which frequently contains various herbs or other components) has a synergistic effect in effecting a cure or reducing toxicity. Network pharmacology targets biological networks and analyzes the links among drugs, targets, and diseases in those networks...
July 7, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28683649/in-vitro-and-in-vivo-delivery-of-artemisinin-loaded-pcl-peg-pcl-micelles-and-its-pharmacokinetic-study
#3
Hamidreza Kheiri Manjili, Hojjat Malvandi, Mir Sajjad Mousavi, Elahe Attari, Hossein Danafar
Artemisinin (ART) is a natural anti-malarial sesquiterpene lactone with anticancer properties, but its application is limited because of its low water solubility. To increase the bioavailability and water solubility of ART, we synthesized three series of poly (ɛ-caprolactone)-poly (ethylene glycol)-poly (ɛ-caprolactone) (PCL-PEG-PCL) tri-block copolymers. The structure of the copolymers was characterized by HNMR, FTIR, DSC and GPC techniques. ART was encapsulated inside micelles by a nanoprecipitation method which leading to the formation of ART/PCL-PEG-PCL micelles...
July 7, 2017: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/28646540/animal-embryotoxicity-studies-of-key-non-artemisinin-antimalarials-and-use-in-women-in-the-first-trimester
#4
REVIEW
Robert L Clark
The World Health Organization currently recommends quinine+clindamycin for use against malaria in the first trimester. This may soon change to recommending artemisinin-based combination therapies (standard duration of dosing = 3 days). The non-artemisinin partner drugs include amodiaquine, lumefantrine, mefloquine, piperaquine, sulfadoxine+pyrimethamine, and pyronaridine. For quinine, clindamycin, and mefloquine and the combinations of sulfadoxine+pyrimethamine and artemether+lumefantrine, there are reports (including studies without internal comparison groups) that combined describe 304 to >1100 exposures of women in the first trimester for each drug with no conclusive evidence of adverse effects on pregnancy at therapeutic doses...
June 24, 2017: Birth defects research
https://www.readbyqxmd.com/read/28645255/haemoglobin-changes-and-risk-of-anaemia-following-treatment-for-uncomplicated-falciparum-malaria-in-sub-saharan-africa
#5
Julien Zwang, Umberto D'Alessandro, Jean-Louis Ndiaye, Abdoulaye A Djimdé, Grant Dorsey, Andreas A Mårtensson, Corine Karema, Piero L Olliaro
BACKGROUND: Anaemia is common in malaria. It is important to quantitate the risk of anaemia and to distinguish factors related to the natural history of disease from potential drug toxicity. METHODS: Individual-patient data analysis based on nine randomized controlled trials of treatments of uncomplicated falciparum malaria from 13 sub-Saharan African countries. Risk factors for reduced haemoglobin (Hb) concentrations and anaemia on presentation and after treatment were analysed using mixed effect models...
June 23, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#6
Annemarie Ackermann, Aysun Çapcı Karagöz, Ali Ghoochani, Michael Buchfelder, Ilker Eyüpoglu, Svetlana B Tsogoeva, Nicolai Savaskan
Gliomas are brain-born tumors with devastating impact on their brain microenvironment. Novel approaches employ multiple combinations of chemical compounds in synthetic hybrid molecules to target malignant tumors. Here, we report on the chemical hybridization approach exemplified by artesunic acid (ARTA) and naturally occurring triterpene betulinic acid (BETA). Artemisinin derived semisynthetic compound artesunic acid (ARTA) and naturally occurring triterpene BETA were used to synthetically couple to the hybrid compound termed 212A...
June 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#7
Sergey O Tcherniuk, Olga Chesnokova, Irina V Oleinikov, Andrew V Oleinikov
Nicotinamide (vitamin B3) - is a water soluble amide derivative of nicotinic acid, which has been used at high doses for a variety of therapeutic applications. However, its antimalarial effect has not been intensively explored. In this work we analysed the effect of nicotinamide alone and in combination with artemisinin, chloroquine andpyrimethamine on the growth of blood stages of P. falciparum. Our results demonstrate that nicotinamide effectively inhibits the growth of blood stage parasites with IC50 of 6...
June 19, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28511056/elimination-of-schistosoma-mansoni-in-infected-mice-by-slow-release-of-artemisone
#8
Daniel Gold, Mohammed Alian, Avraham Domb, Yara Karawani, Maysa Jbarien, Jacques Chollet, Richard K Haynes, Ho Ning Wong, Viola Buchholz, Andreas Greiner, Jacob Golenser
The current treatment of schistosomiasis is based on the anti-helminthic drug praziquantel (PZQ). PZQ affects only the adult stages of schistosomes. In addition, resistance to PZQ is emerging. We suggest a drug, which could serve as a potential alternative or complement to PZQ, and as a means of treating infections at earlier, pre-granuloma stage. Derivatives of the peroxidic antimalarial drug artemisinin have been indicated as alternatives, because both plasmodia and schistosomes are blood-feeding parasites...
August 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28466458/rip1-dependent-reactive-oxygen-species-production-executes-artesunate-induced-cell-death-in-renal-carcinoma-caki-cells
#9
Anil Kumar Chauhan, Kyoung-Jin Min, Taeg Kyu Kwon
Artesunate is a well-known anti-malarial drug originated from artemisinin as a Chinese herb and has been reported to have anti-cancer potential in many cancer cells. In the present study, we examined the efficacy of artesunate against the renal carcinoma Caki cells and explored its mechanism of cytotoxicity. A steep decline in cell viability within 18 h was recorded upon artesunate exposure, but pretreatment of z-VAD-FMK had no effect on the loss of the cell viability by artesunate. On the other hand, necrostatin-1 pretreatment and knockdown of RIP-1 significantly reduced the cytotoxicity of artesunate against Caki cell...
May 2, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28454894/the-antimalarial-drug-artemisinin-induces-an-additional-sod1-supressible-anti-mitochondrial-action-in-yeast
#10
Chen Sun, Bing Zhou
The molecular action of artemisinins (ARTs) is not well understood. To determine the molecular and cellular basis that might underlie their differential effects observed in anti-malarial and anti-cancer studies, we utilized the yeast Saccharomyces cerevisiae to examine their toxicity profiles and properties. Previously we reported that while both low levels (2-8μM) of artemisinin (ART) and dihydroartemisinin (DHA) partly depolarize the mitochondrial membranes, inhibiting yeast growth on non-fermentable media, only DHA at moderate levels (such as 40μM) potently represses yeast growth on fermentable media via a heme-mediated pathway...
April 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28447781/artemisinin-protects-retinal-neuronal-cells-against-oxidative-stress-and-restores-rat-retinal-physiological-function-from-light-exposed-damage
#11
Fengxia Yan, Haitao Wang, Yang Gao, Jiangping Xu, Wenhua Zheng
Oxidative stress plays a key role in the pathogenesis of age-related macular degeneration (AMD), a leading cause of severe visual loss and blindness in the aging population which lacks any effective treatments currently. In this study, artemisinin, a well-known antimalarial drug was found to suppress hydrogen peroxide (H2O2)-induced cell death in retinal neuronal RGC-5 cells. Artemisinin, in the therapeutically relevant dosage, concentration-dependently attenuated the accumulation of intracellular reactive oxygen species (ROS), increased mitochondrial membrane potential and decreased cell apoptosis in RGC-5 cells induced by H2O2...
August 16, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28391183/artemisinin-protects-pc12-cells-against-%C3%AE-amyloid-induced-apoptosis-through-activation-of-the-erk1-2-signaling-pathway
#12
Zhiwen Zeng, Jinying Xu, Wenhua Zheng
Accumulating evidence displays that an abnormal deposition of amyloid beta-peptide (Aβ) is the primary cause of the pathogenesis of Alzheimer's disease (AD). And therefore the elimination of Aβ is regarded as an important strategy for AD treatment. The discovery of drug candidates using culture neuronal cells against Aβ peptide toxicity is believed to be an effective approach to develop drug for the treatment of AD patients. We have previously showed that artemisinin, a FDA-approved anti-malaria drug, has neuroprotective effects recently...
August 2017: Redox Biology
https://www.readbyqxmd.com/read/28368011/a-mitochondria-targeting-artemisinin-derivative-with-sharply-increased-antitumor-but-depressed-anti-yeast-and-anti-malaria-activities
#13
Chen Sun, Yu Cao, Pan Zhu, Bing Zhou
The potent anti-malarial drug artemisinins are additionally anti-tumorigenic and inhibitory to yeast growth. The action mechanism of artemisinins, however, is not well understood. Heme and mitochondrial membrane are both suggested to be involved in the action of artemisinins. Because heme is also synthesized in the mitochondrion, mitochondria appear to be a critical organelle for artemisinins' activities. In this study, we synthesized a mitochondria-targeting artemisinin derivative by conjugating triphenylphosphonium (TPP) to artelinic acid (ARTa)...
April 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28366726/cancer-combination-therapies-with-artemisinin-type-drugs
#14
REVIEW
Thomas Efferth
Artemisia annua L. is a Chinese medicinal plant, which is used throughout Asia and Africa as tea or press juice to treat malaria. The bioactivity of its chemical constituent, artemisinin is, however, much broader. We and others found that artemisinin and its derivatives also exert profound activity against tumor cells in vitro and in vivo. Should artemisinin-type drugs be applied routinely in clinical oncology in the future, then it should probably be as part of combination therapy regimens rather than as monotherapy...
September 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28361857/artemisinin-modulating-effect-on-human-breast-cancer-cell-lines-with-different-sensitivity-to-cytostatics
#15
V F Chekhun, N Yu Lukianova, T V Borikun, T V Zadvorny, A Mokhir
AIM: To explore effects of Artemisinin on a series of breast cancer cells with different sensitivity to typical cytotoxic drugs (doxorubicin - Dox; cisplatin - DDP) and to investigate possible artemisinin-induced modification of the mechanisms of drug resistance. MATERIALS AND METHODS: The study was performed on wild-type breast cancer MCF-7 cell line (MCF-7/S) and its two sublines MCF-7/Dox and MCF-7/DDP resistant to Dox and DDP, respectively. The cells were treated with artemisinin and iron-containing magnetic fluid...
March 2017: Experimental Oncology
https://www.readbyqxmd.com/read/28359890/artemisinin-loaded-chitosan-magnetic-nanoparticles-for-theefficient-targeting-to-the-breast-cancer
#16
Subramanian Natesan, Chandrasekar Ponnusamy, Abimanyu Sugumaran, Senthilkumar Chelladurai, Sharavanan Shanmugam Palaniappan, Rajaguru Palanichamy
Artemisinin, a natural anti-malarial agent, also possesses anti-proliferative and anti-angiogenic activity in cancer cells with very low toxicity to normal healthy cells. Drug loaded magnetic nanoparticlesby using external magnetic field could selectively accumulate the drug at the target site and thereby reduce the doses required to achieve therapeutic concentration which may otherwise produce serious side effects on healthy cells. In the present study the artemisinin magnetic nanoparticles were successfully formulated using chitosan by ionic-gelation method...
March 27, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28356736/nanoliposomal-artemisinin-for-the-treatment-of-murine-visceral-leishmaniasis
#17
Muzamil Y Want, Mohammad Islammudin, Garima Chouhan, Hani A Ozbak, Hassan A Hemeg, Asoke P Chattopadhyay, Farhat Afrin
Visceral leishmaniasis (VL) is a fatal, vector-borne disease caused by the intracellular protozoa of the genus Leishmania. Most of the therapeutics for VL are toxic, expensive, or ineffective. Sesquiterpenes are a new class of drugs with proven antimicrobial and antiviral activities. Artemisinin is a sesquiterpene lactone with potent antileishmanial activity, but with limited access to infected cells, being a highly lipophilic molecule. Association of artemisinin with liposome is a desirable strategy to circumvent the problem of poor accessibility, thereby improving its efficacy, as demonstrated in a murine model of experimental VL...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28289029/are-antimalarial-hybrid-molecules-a-close-reality-or-a-distant-dream
#18
REVIEW
Drishti Agarwal, Rinkoo D Gupta, Satish K Awasthi
Emergence of drug-resistant Plasmodium falciparum strains has led to a situation of haste in the scientific and pharmaceutical communities. Hence, all their efforts are redirected toward finding alternative chemotherapeutic agents that are capable of combating multidrug-resistant parasite strains. In light of this situation, scientists have come up with the concept of hybridization of two or more active pharmacophores into a single chemical entity, resulting in "antimalarial hybrids." The approach has been applied widely for generation of lead compounds against deadly diseases such as cancer and AIDS, with a proven potential for use as novel drugs, but is comparatively new in the sphere of antimalarial drug discovery...
May 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28287416/novel-pharmacological-activity-of-artesunate-and-artemisinin-their-potential-as-anti-tubercular-agents
#19
Won Hyung Choi
Tuberculosis is a major infectious disease that globally causes the highest human mortality. From this aspect, this study was carried out to evaluate novel pharmacological activities/effects of artesunate and artemisinin causing anti-tubercular activity/effects against Mycobacterium tuberculosis (Mtb). The anti-Mtb activities/effects of artesunate and artemisinin were evaluated using different anti-Mtb indicator assays, such as the resazurin microtiter assay, the Mycobacteria Growth Indicator Tube (MGIT) 960 system assay, and the Ogawa slant medium assay, as well as in vivo tests...
March 10, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28273638/antimalarial-activity-and-safety-assessment-of-flueggea-virosa-leaves-and-its-major-constituent-with-special-emphasis-on-their-mode-of-action
#20
Shiv Vardan Singh, Ashan Manhas, Yogesh Kumar, Sonali Mishra, Karuna Shanker, Feroz Khan, Kumkum Srivastava, Anirban Pal
A clinical emergency stands due to the appearance of drug resistant Plasmodium strains necessitate novel and effective antimalarial chemotypes, where plants seem as the prime option, especially after the discovery of quinine and artemisinin. The present study was aimed towards bioprospecting leaves of Flueggea virosa for its antimalarial efficacy and active principles. Crude hydro-ethanolic extract along with solvent derived fractions were tested in vitro against Plasmodium falciparum CQ sensitive (3D7) and resistant (K1) strains, where all the fractions exhibited potential activity (IC50 values <10μg/mL) against both the strains...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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