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Dihydroartemisinin

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https://www.readbyqxmd.com/read/28329368/intermittent-preventive-treatment-with-dihydroartemisinin-piperaquine-for-the-prevention-of-malaria-among-hiv-infected-pregnant-women
#1
Paul Natureeba, Abel Kakuru, Mary Muhindo, Eric Littmann, Teddy Ochieng, John Ategeka, Catherine A Koss, Albert Plenty, Edwin D Charlebois, Tamara D Clark, Bridget Nzarubara, Miriam Nakalembe, Deborah Cohan, Gabrielle Rizzuto, Atis Muehlenbachs, Theodore Ruel, Prasanna Jagannathan, Diane V Havlir, Moses R Kamya, Grant Dorsey
Background.: Daily trimethoprim-sulfamethoxazole (TMP-SMX) and insecticide treated nets (ITNs) remain the main interventions for prevention of malaria in HIV-infected pregnant women in Africa. However, antifolate and pyrethroid resistance threaten the effectiveness of these intervention and new ones are needed. Methods.: We conducted a double-blind randomized placebo-controlled trial comparing daily TMP-SMX plus monthly dihydroartemisinin-piperaquine (DP) to daily TMP-SMX alone in HIV-infected pregnant women in an area of Uganda where indoor residual spraying of insecticide (IRS) had recently been implemented...
February 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28322709/treatment-failure-of-dihydroartemisinin-piperaquine-for-plasmodium-falciparum-malaria-vietnam
#2
Bui Quang Phuc, Charlotte Rasmussen, Tran Thanh Duong, Le Than Dong, Mai Anh Loi, Didier Ménard, Joel Tarning, Dorina Bustos, Pascal Ringwald, Gawrie Loku Galappaththy, Nguyen Quang Thieu
We conducted a study in Binh Phuoc, Vietnam, in 2015 on the therapeutic efficacy of dihydroartemisinin/piperaquine for Plasmodium falciparum malaria. A high number of treatment failures (14/40) was found, and piperaquine resistance in Vietnam was confirmed. A change in the malaria treatment policy for Vietnam is in process.
April 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28302108/confirmation-of-plasmodium-falciparum-in-vitro-resistance-to-monodesethylamodiaquine-and-chloroquine-in-dakar-senegal-in-2015
#3
Silman Diawara, Marylin Madamet, Mame Bou Kounta, Gora Lo, Khalifa Ababacar Wade, Aminata Nakoulima, Raymond Bercion, Rémy Amalvict, Mamadou Wague Gueye, Bécaye Fall, Bakary Diatta, Bruno Pradines
BACKGROUND: In response to increasing resistance to anti-malarial drugs, Senegal adopted artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria in 2006. However, resistance of Plasmodium falciparum parasites to artemisinin derivatives, characterized by delayed parasite clearance after treatment with ACT or artesunate monotherapy, has recently emerged and rapidly spread in Southeast Asia. After 10 years of stability with rates ranging from 5.6 to 11...
March 16, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28261759/dihydroartemisinin-sensitizes-human-lung-adenocarcinoma-a549-cells-to-arsenic-trioxide-via-apoptosis
#4
Hongyu Chen, Shiyan Gu, Huangmei Dai, Xinyang Li, Zunzhen Zhang
Recent studies have shown that arsenic trioxide (ATO) is an effective anti-cancer drug for treatment of acute promyelocytic leukemia and other types of human cancer. However, we have found that lung cancer cells constantly develop a high level of resistance to ATO. In this study, we have explored a possibility of combination of dihydroartemisinin (DHA) and ATO treatments to reduce ATO resistance of lung cancer cells. We determined the combinatory effects of DHA and ATO on cytotoxicity of human lung adenocarcinoma (A549) cells...
March 6, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28259625/characterization-of-the-selective-alkylation-site-in-hemoglobin-a-by-dihydroartemisinin-with-tandem-mass-spectrometry
#5
Khomsan Tiensomjitr, Samran Prabpai, Palangpon Kongsaeree
The reaction between the antimalarial drug dihydroartemisinin (DHA) and hemoglobin A (HbA) was investigated in vitro. A fluorescein-tagged artemisinin analog reacted with HbA and fluorescent HbA-drug adducts could be visualized on SDS-PAGE to confirm stable covalent reaction adducts and necessity of the endoperoxide moiety and Fe(II). Mass spectrometric analyses revealed that DHA favourably alkylated protein part rather than heme and the modification site was identified to be at Tyr35 of the beta globin chain...
March 1, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28254675/from-ancient-herb-to-modern-drug-artemisia-annua-and-artemisinin-for-cancer-therapy
#6
REVIEW
Thomas Efferth
Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptomes (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016...
February 28, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28247889/uptake-of-silver-nanoparticles-by-dha-treated-cancer-cells-examined-by-surface-enhanced-raman-spectroscopy-in-a-microfluidic-chip
#7
Zhimin Zhai, Fengqiu Zhang, Xiangyu Chen, Jie Zhong, Gang Liu, Yangchao Tian, Qing Huang
This paper reports on the synthesis and application of biocompatible and sensitive SERS nanoparticles for the study of uptake of nanoparticles into living cells in a microfluidic chip through surface-enhanced Raman spectroscopy (SERS). The nanoparticles were fabricated as beta-cyclodextrin-coated silver nanoparticles (Ag@CD NPs) modified with para-aminothiophenol (p-ATP) and folic acid (FA) on the surface. The p-ATP molecules act as the Raman reporter while the FA tags have high affinity for folate receptors (FR) that are over-expressed on the surface cancerous cells, so that the nanoparticles can enter the cells and be monitored by the Raman reporter...
March 1, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28242661/prediction-of-improved-antimalarial-chemoprevention-with-weekly-dosing-of-dihydroartemisinin-piperaquine
#8
Jesmin Permala, Joel Tarning, François Nosten, Nicholas J White, Mats O Karlsson, Martin Bergstrand
Intermittent preventive treatment (IPT) is used to reduce malaria morbidity and mortality, especially in vulnerable groups such as children and pregnant women. IPT with the fixed dose combination of piperaquine (PQ) and dihydroartemisinin (DHA) is being evaluated as a potential mass treatment to control and eliminate artemisinin resistant falciparum malaria. This study explored alternative DHA-PQ adult dosing regimens compared to the monthly adult dosing regimen currently being studied in clinical trials. A time-to-event model describing the concentration-effect relationship of preventive DHA-PQ administration was used to explore the potential clinical efficacy of once weekly adult dosing regimens...
February 27, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28218680/application-of-the-triazolization-reaction-to-afford-dihydroartemisinin-derivatives-with-anti-hiv-activity
#9
Sampad Jana, Shabina Iram, Joice Thomas, Muhammad Qasim Hayat, Christophe Pannecouque, Wim Dehaen
Artemisinin and synthetic derivatives of dihydroartemisinin are known to possess various biological activities. Post-functionalization of dihydroartemisinin with triazole heterocycles has been proven to lead to enhanced therapeutic potential. By using our newly developed triazolization strategy, a library of unexplored fused and 1,5-disubstituted 1,2,3-triazole derivatives of dihydroartemisinin were synthesized in a single step. All these newly synthesized compounds were characterized and evaluated for their anti-HIV (Human Immunodeficiency Virus) potential in MT-4 cells...
February 17, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28213434/malaria-during-pregnancy
#10
Michal Fried, Patrick E Duffy
One hundred and twenty-five million women in malaria-endemic areas become pregnant each year (see Dellicour et al. PLoS Med7: e1000221 [2010]) and require protection from infection to avoid disease and death for themselves and their offspring. Chloroquine prophylaxis was once a safe approach to prevention but has been abandoned because of drug-resistant parasites, and intermittent presumptive treatment with sulfadoxine-pyrimethamine, which is currently used to protect pregnant women throughout Africa, is rapidly losing its benefits for the same reason...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28208619/akt-axis-mir-21-and-reck-play-pivotal-roles-in-dihydroartemisinin-killing-malignant-glioma-cells
#11
Ying-Ying Shao, Tao-Lan Zhang, Lan-Xiang Wu, He-Cun Zou, Shuang Li, Jin Huang, Hong-Hao Zhou
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is known to play important roles in inhibiting proliferation rate, inducing apoptosis, as well as hindering the metastasis and invasion of glioma cells, but the underlying mechanisms are still unclear so far. In this study, methyl thiazolyl tetrazolium (MTT), colony-forming, wound healing, invasion, and apoptosis assays were performed to investigate the effect of DHA on malignant glioma cells. Results showed that DHA induced apoptosis of malignant glioma cells through Protein Kinase B (AKT) axis, induced death of malignant glioma cells by downregulating miR-21, and inhibited the invasion of malignant glioma cells corresponding with up-regulation of the reversion-inducing-cysteine-rich protein with kazal motifs (RECK)...
February 10, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28195463/target-elucidation-by-cocrystal-structures-of-nadh-ubiquinone-oxidoreductase-of-plasmodium-falciparum-pfndh2-with-small-molecule-to-eliminate-drug-resistant-malaria
#12
Yiqing Yang, You Yu, Xiaolu Li, Jing Li, Yue Wu, Jie Yu, Jingpeng Ge, Zhenghui Huang, Lubin Jiang, Yu Rao, Maojun Yang
Drug-resistant malarial strains have been continuously emerging recently, which posts a great challenge for the global health. Therefore, new antimalarial drugs with novel targeting mechanisms are urgently needed for fighting drug-resistant malaria. NADH-ubiquinone oxidoreductase of Plasmodium falciparum (PfNDH2) represents a viable target for antimalarial drug development. However, the absence of structural information on PfNDH2 limited rational drug design and further development. Herein, we report high resolution crystal structures of the PfNDH2 protein for the first time in Apo-, NADH-, and RYL-552 (a new inhibitor)-bound states...
February 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28193647/piperaquine-population-pharmacokinetics-and-cardiac-safety-in-cambodia
#13
Pattaraporn Vanachayangkul, Chanthap Lon, Michele Spring, Sommethy Sok, Winita Ta-Aksorn, Chanikarn Kodchakorn, Sut-Thang Pann, Soklyda Chann, Mali Ittiverakul, Sabaithip Sriwichai, Nillawan Buathong, Worachet Kuntawunginn, Mary So, Theng Youdaline, Erin Milner, Mariusz Wojnarski, Charlotte Lanteri, Jessica Manning, Satharath Prom, Mark Haigney, Louis Cantilena, David Saunders
Despite rising resistance, dihydroartemisinin-piperaquine (DP) remains a first line therapy for uncomplicated malaria in many parts of Cambodia. While generally well-tolerated as a 3-day regimen, compressed 2-day regimens were associated with treatment-limiting cardiac repolarization effects in a recent clinical trial. To better estimate the risks of piperaquine concentration on QT interval prolongation, we pooled data from 3 randomized clinical trials between 2010 and 2014 in northern Cambodia. A population pharmacokinetic model was developed to compare exposure-response relationships between 2-day (2DP) and 3-day (3DP) regimens while accounting for differences in regimen and sample collection times between studies...
February 13, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28189106/application-of-sequential-factorial-design-and-orthogonal-array-composite-design-oacd-to-study-combination-of-5-prostate-cancer-drugs
#14
Xiaolong Jia, Yiyang Li, Alok Sharma, Yulong Li, Guohai Xie, Guoyao Wang, Junhui Jiang, Yue Cheng, Xianting Ding
Prostate cancer is one of the most common cancers among men in the United States. It is also a major leading cause of cancer death among men of all races. In order to treat prostate cancer, drug combinations are often applied. Drug combinations target at different pathways of cells can potentially lead to higher efficacy and lower toxicity due to drug synergy. In this paper, we sequentially applied a two-level design and a follow-up orthogonal array composite design (OACD) to investigate combinations of five anti-cancer drugs, namely, doxorubicin, docetaxel, paclitaxel, cis-dichlorodiamine platinum and dihydroartemisinin...
February 4, 2017: Computational Biology and Chemistry
https://www.readbyqxmd.com/read/28187497/antiretroviral-therapy-with-efavirenz-accentuates-pregnancy-associated-reduction-of-dihydroartemisinin-piperaquine-exposure-during-malaria-chemoprevention
#15
Richard Kajubi, Liusheng Huang, Prasanna Jagannathan, Nona Chamankhah, Moses Were, Theodore Ruel, Catherine A Koss, Abel Kakuru, Norah Mwebaza, Moses Kamya, Diane Havlir, Grant Dorsey, Philip J Rosenthal, Francesca T Aweeka
Dihydroartemisinin (DHA)-piperaquine is promising for malaria chemoprevention in pregnancy. We assessed impacts of pregnancy and efavirenz-based antiretroviral therapy on exposure to DHA and piperaquine in pregnant Ugandan women. Intensive sampling was performed at 28 weeks gestation in 31 HIV-uninfected pregnant women, in 27 HIV-infected pregnant women receiving efavirenz, and in 30 HIV-uninfected non-pregnant women. DHA peak concentration and area under the concentration time curve (AUC0-8hr ) were 50% and 47% lower, respectively, and piperaquine AUC0-21d was 40% lower in pregnant women compared to non-pregnant women...
February 10, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28182780/farnesylthiosalicylic-acid-sensitizes-hepatocarcinoma-cells-to-artemisinin-derivatives
#16
Liping Wu, Yilin Pang, Guiqi Qin, Gaina Xi, Shengnan Wu, Xiaoping Wang, Tongsheng Chen
Dihydroartemisinin (DHA) and artesunate (ARS), two artemisinin derivatives, have efficacious anticancer activities against human hepatocarcinoma (HCC) cells. This study aims to study the anticancer action of the combination treatment of DHA/ARS and farnesylthiosalicylic acid (FTS), a Ras inhibitor, in HCC cells (Huh-7 and HepG2 cell lines). FTS pretreatment significantly enhanced DHA/ARS-induced phosphatidylserine (PS) externalization, Bak/Bax activation, mitochondrial membrane depolarization, cytochrome c release, and caspase-8 and -9 activations, characteristics of the extrinsic and intrinsic apoptosis...
2017: PloS One
https://www.readbyqxmd.com/read/28170391/haemolysis-in-g6pd-heterozygous-females-treated-with-primaquine-for-plasmodium-vivax-malaria-a-nested-cohort-in-a-trial-of-radical-curative-regimens
#17
Cindy S Chu, Germana Bancone, Kerryn A Moore, Htun Htun Win, Niramon Thitipanawan, Christina Po, Nongnud Chowwiwat, Rattanaporn Raksapraidee, Pornpimon Wilairisak, Aung Pyae Phyo, Lily Keereecharoen, Stéphane Proux, Prakaykaew Charunwatthana, François Nosten, Nicholas J White
BACKGROUND: Radical cure of Plasmodium vivax malaria with 8-aminoquinolines (primaquine or tafenoquine) is complicated by haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD heterozygous females, because of individual variation in the pattern of X-chromosome inactivation (Lyonisation) in erythroid cells, may have low G6PD activity in the majority of their erythrocytes, yet are usually reported as G6PD "normal" by current phenotypic screening tests...
February 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28154599/effect-of-stents-coated-with-artemisinin-or-dihydroartemisinin-in-a-porcine-coronary-restenosis-model
#18
Suyoung Jang, Myung Ho Jeong, Kyung Seob Lim, In Ho Bae, Jun-Kyu Park, Dae Sung Park, Jae Won Shim, Jung Ha Kim, Hyun Kuk Kim, Doo Sun Sim, Young Joon Hong, Youngkeun Ahn, Jung Chaee Kang
BACKGROUND AND OBJECTIVES: Artemisinin and dihydroartemisinin are drugs used to treat malaria. These drugs suppress inflammatory reactions. The aim of this study was to examine the anti-intima hyperplasia effect of a novel drug-eluting stent with artemisinin or dihydroartemisinin in a porcine coronary restenosis model. MATERIALS AND METHODS: Pigs were randomized into four groups; in the first, the coronary arteries (20 pigs, a total of 40 coronary arteries, with 10 coronary arteries in each group) was implanted with bare metal stents (BMS, n=10); the second group was given polymer-coated stents (PCS, n=10); the third group was treated with artemisinin-eluting stents (AES, n=10); and the fourth group was given dihydroartemisinin-eluting stents (DAES, n=10)...
January 2017: Korean Circulation Journal
https://www.readbyqxmd.com/read/28153004/efficacy-of-artemether-lumefantrine-artesunate-amodiaquine-and-dihydroartemisinin-piperaquine-for-treatment-of-uncomplicated-plasmodium-falciparum-malaria-in-angola-2015
#19
Mateusz M Plucinski, Pedro Rafael Dimbu, Aleixo Panzo Macaia, Carolina Miguel Ferreira, Claudete Samutondo, Joltim Quivinja, Marília Afonso, Richard Kiniffo, Eliane Mbounga, Julia S Kelley, Dhruviben S Patel, Yun He, Eldin Talundzic, Denise O Garrett, Eric S Halsey, Venkatachalam Udhayakumar, Pascal Ringwald, Filomeno Fortes
BACKGROUND: Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether-lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013. METHODS: During January-June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate-amodiaquine (ASAQ), or dihydroartemisinin-piperaquine (DP)...
February 2, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28151566/efficacy-of-artesunate-sulphadoxine-pyrimethamine-and-artemether-lumefantrine-and-dhfr-and-dhps-mutations-in-somalia-evidence-for-updating-the-malaria-treatment-policy
#20
Marian Warsame, Abdikarim Hussein Hassan, Abdillahi Mohamed Hassan, Abdulkadir Mohamed Arale, Ali Mohamed Jibril, Said Abdulkadir Mohamud, Amy Barrette, Abdikarim Yusuf Muse, Fahmi Essa Yusuf, Rania A Nada, Jamal Ghilan Hefzullah Amran
OBJECTIVE: To determine the therapeutic efficacy of artesunate + sulphadoxine/pyrimethamine (AS + SP) and artemether + lumefantrine (AL), and to investigate the presence of molecular mutations associated with resistance, to inform national malaria treatment policy. METHODS: One-arm prospective studies were conducted in three study sites in Somalia in 2013 and 2015 to evaluate the efficacy of AS + SP and AL among patients with uncomplicated falciparum malaria. Outcomes included clinical and parasitological response over 28 days, and the presence of dihydrofolate reductase (dfhr) and dihydropteroate synthase (dhps) and mutations...
February 2, 2017: Tropical Medicine & International Health: TM & IH
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