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https://www.readbyqxmd.com/read/28637008/cytotoxic-profiling-of-artesunic-and-betulinic-acids-and-their-synthetic-hybrid-compound-on-neurons-and-gliomas
#1
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/28636884/major-achievements-of-evidence-based-traditional-chinese-medicine-in-treating-major-diseases
#2
REVIEW
Jung Chao, Yuntao Dai, Robert Verpoorte, Wing Lam, Yung-Chi Cheng, Li-Heng Pao, Wei Zhang, Shilin Chen
A long history of use and extensive documentation of the clinical practices of traditional Chinese medicine resulted in a considerable number of classical preparations, which are still widely used. This heritage of our ancestors provides a unique resource for drug discovery. Already, a number of important drugs have been developed from traditional medicines, which in fact form the core of Western pharmacotherapy. Therefore, this article discusses the differences in drug development between traditional medicine and Western medicine...
June 18, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28635296/benzoxaborole-antimalarial-agents-part-5-lead-optimization-of-novel-amide-pyrazinyloxy-benzoxaboroles-and-identification-of-a-preclinical-candidate
#3
Yong-Kang Zhang, Jacob J Plattner, Eric E Easom, Robert Toms Jacobs, Denghui Guo, Yvonne R Freund, Pamela Berry, Vic Ciaravino, John C L Erve, Philip J Rosenthal, Brice Campo, Francisco-Javier Gamo, Laura M Sanz, Jianxin Cao
Carboxamide pyrazinyloxy benzoxaboroles were investigated with the goal to identify a molecule with satisfactory antimalarial activity, physicochemical properties, pharmacokinetic profile, in vivo efficacy, and safety profile. This optimization effort discovered 46, which met our target candidate profile. Compound 46 had excellent activity against cultured Plasmodium falciparum, and in vivo against P. falciparum and P. berghei in infected mice. It exhibited good PK properties in mouse, rat and dog. It was highly active against other eleven P...
June 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28634831/malaria-2017-update-on-the-clinical-literature-and-management
#4
REVIEW
Johanna P Daily
PURPOSE OF REVIEW: Malaria is a prevalent disease in travelers to and residents of malaria-endemic regions. Health care workers in both endemic and non-endemic settings should be familiar with the latest evidence for the diagnosis, management and prevention of malaria. This article will discuss the recent malaria epidemiologic and medical literature to review the progress, challenges, and optimal management of malaria. RECENT FINDINGS: There has been a marked decrease in malaria-related global morbidity and mortality secondary to malaria control programs over the last few decades...
June 20, 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28633997/nicotinamide-inhibits-the-growth-of-p-falciparum-and-enhances-the-antimalarial-effect-of-artemisinin-chloroquine-and-pyrimethamine
#5
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 17, 2017: Molecular and Biochemical Parasitology
https://www.readbyqxmd.com/read/28625144/detection-of-poor-quality-artemisinin-based-combination-therapy-act-medicines-marketed-in-benin-using-simple-and-advanced-analytical-techniques
#6
Achille Yemoa, Védaste Habyalimana, Jérémie K Mbinze, Victoria Crickboom, Benjamin Muhigirwa, Agnès Ngoya, Pierre-Yves Sacré, Fernand Gbaguidi, Joëlle Quetin-Leclercq, Philippe Hubert, Roland D Marini
BACKGROUND: Poor quality antimalarial medicines still represent a threat to the public health, especially in Sub-Saharan Africa who bears a disproportionate share of the global burden of malaria. It is essential and urgent to strengthen mechanisms against counterfeit medicines. One of the approaches is regular market surveillance through quality controls. METHODS: 12 samples of artemether/lumefantrine were collected from formal and informal drug sellers in Cotonou (Benin) as well as additional other similar samples from Rwanda (13 samples) and from D...
June 15, 2017: Current Drug Safety
https://www.readbyqxmd.com/read/28620813/an-in-silico-insight-into-the-substrate-binding-characteristics-of-the-active-site-of-amorpha-4-11-diene-synthase-a-key-enzyme-in-artemisinin-biosynthesis
#7
Habib Eslami, Seyed Kaveh Mohtashami, Maryam Taghavi Basmanj, Maryam Rahati, Hamzeh Rahimi
The enzyme amorphadiene synthase (ADS) conducts the first committed step in the biosynthetic conversion of the substrate farnesyl pyrophosphate (FPP) to artemisinin, which is a highly effective natural product against multidrug-resistant strains of malaria. Due to the either low abundance or low turn-over rate of the enzyme, obtaining artemisinin from both natural and synthetic sources is costly and laborious. In this in silico study, we strived to elucidate the substrate binding site specificities of the ADS, with the rational that unraveling enzyme features paves the way for enzyme engineering to increase synthesis rate...
July 2017: Journal of Molecular Modeling
https://www.readbyqxmd.com/read/28615026/engaging-the-private-sector-in-malaria-surveillance-a-review-of-strategies-and-recommendations-for-elimination-settings
#8
Adam Bennett, Anton L V Avanceña, Jennifer Wegbreit, Chris Cotter, Kathryn Roberts, Roly Gosling
BACKGROUND: In malaria elimination settings, all malaria cases must be identified, documented and investigated. To facilitate complete and timely reporting of all malaria cases and effective case management and follow-up, engagement with private providers is essential, particularly in settings where the private sector is a major source of healthcare. However, research on the role and performance of the private sector in malaria diagnosis, case management and reporting in malaria elimination settings is limited...
June 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28615016/ex-vivo-susceptibility-and-genotyping-of-plasmodium-falciparum-isolates-from-pikine-senegal
#9
Aminata Mbaye, Amy Gaye, Baba Dieye, Yaye D Ndiaye, Amy K Bei, Muna Affara, Awa B Deme, Mamadou S Yade, Khadim Diongue, Ibrahima M Ndiaye, Tolla Ndiaye, Mouhamed Sy, Ngayo Sy, Ousmane Koita, Donald J Krogstad, Sarah Volkman, Davis Nwakanma, Daouda Ndiaye
BACKGROUND: The monitoring of Plasmodium falciparum sensitivity to anti-malarial drugs is a necessity for effective case management of malaria. This species is characterized by a strong resistance to anti-malarial drugs. In Senegal, the first cases of chloroquine resistance were reported in the Dakar region in 1988 with nearly 7% population prevalence, reaching 47% by 1990. It is in this context that sulfadoxine-pyrimethamine temporarily replaced chloroquine as first line treatment in 2003, pending the introduction of artemisinin-based combination therapy in 2006...
June 14, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28610396/nanoparticle-delivery-of-artesunate-enhances-the-anti-tumor-efficiency-by-activating-mitochondria-mediated-cell-apoptosis
#10
Rui Liu, Xiwei Yu, Chang Su, Yijie Shi, Liang Zhao
Artemisinin and its derivatives were considered to exert a broad spectrum of anti-cancer activities, and they induced significant anti-cancer effects in tumor cells. Artemisinin and its derivatives could be absorbed quickly, and they were widely distributed, selectively killing tumor cells. Since low concentrations of artesunate primarily depended on oncosis to induce cell death in tumor cells, its anti-tumor effects were undesirable and limited. To obtain better anti-tumor effects, in this study, we took advantage of a new nanotechnology to design novel artesunate-loaded bovine serum albumin nanoparticles to achieve the mitochondrial accumulation of artesunate and induce mitochondrial-mediated apoptosis...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28609442/the-us-president-s-malaria-initiative-and-under-5-child-mortality-in-sub-saharan-africa-a-difference-in-differences-analysis
#11
Aleksandra Jakubowski, Sally C Stearns, Margaret E Kruk, Gustavo Angeles, Harsha Thirumurthy
BACKGROUND: Despite substantial financial contributions by the United States President's Malaria Initiative (PMI) since 2006, no studies have carefully assessed how this program may have affected important population-level health outcomes. We utilized multiple publicly available data sources to evaluate the association between introduction of PMI and child mortality rates in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We used difference-in-differences analyses to compare trends in the primary outcome of under-5 mortality rates and secondary outcomes reflecting population coverage of malaria interventions in 19 PMI-recipient and 13 non-recipient countries between 1995 and 2014...
June 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28606818/investigating-unlicensed-retail-drug-vendors-preparedness-and-knowledge-about-malaria-an-exploratory-study-in-rural-uganda
#12
Eric Liow, Rosemin Kassam, Richard Sekiwunga
BACKGROUND: Despite major efforts to increase the uptake of preventive measures and timely use of the first line antimalarial treatment artemisinin-based combination therapies (ACT), Uganda continues to fall short of meeting its national malaria control targets. One of the challenges has been scaling up effective measures in rural and remote areas where the unlicensed private retail sector remains the first point of contact and a common source of treatment. The current paper discusses unlicensed vendors' (1) training related to malaria case management for children aged five and under, and (2) knowledge related to the cause of malaria, preventive measures, common signs, and symptoms, diagnostic procedures, and best treatment options...
June 9, 2017: Acta Tropica
https://www.readbyqxmd.com/read/28605472/safety-and-efficacy-of-adding-a-single-low-dose-of-primaquine-to-the-treatment-of-adult-patients-with-plasmodium-falciparum-malaria-in-senegal-to-reduce-gametocyte-carriage-a-randomized-controlled-trial
#13
Roger C Tine, Khadime Sylla, Babacar T Faye, Eugenie Poirot, Fatou B Fall, Doudou Sow, Duolao Wang, Magatte Ndiaye, Jean Louis Ndiaye, Babacar Faye, Brian Greenwood, Oumar Gaye, Paul Milligan
Introduction.: More information is needed about the safety of low-dose primaquine in populations where G6PD deficiency is common. Methods.: Adults with Plasmodium falciparum malaria were randomized to receive 1 of 3 artemisinin combination therapies (ACTs) with or without primaquine (0.25 mg/kg). Glucose-6-phosphate dehydrogenase (G6PD) status was determined using a rapid test. Patients were followed for 28 days to record hemoglobin concentration, adverse events, and gametocyte carriage...
June 12, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/28599096/proteases-as-antimalarial-targets-strategies-for-genetic-chemical-and-therapeutic-validation
#14
REVIEW
Edgar Deu
Malaria is a devastating parasitic disease affecting half of the world's population. The rapid emergence of resistance against new antimalarial drugs, including artemisinin-based therapies, has made the development of drugs with novel mechanisms of action extremely urgent. Proteases are enzymes proven to be well suited for target-based drug development due to our knowledge of their enzymatic mechanisms and active site structures. More importantly, Plasmodium proteases have been shown to be involved in a variety of pathways that are essential for parasite survival...
June 9, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28594879/molecular-surveillance-of-plasmodium-falciparum-resistance-to-artemisinin-based-combination-therapies-in-the-democratic-republic-of-congo
#15
Dieudonné Makaba Mvumbi, Thierry Lengu Bobanga, Jean-Marie Ntumba Kayembe, Georges Lelo Mvumbi, Hippolyte Nani-Tuma Situakibanza, Françoise Benoit-Vical, Pierrette Melin, Patrick De Mol, Marie-Pierre Hayette
Malaria is a major public health problem in the Democratic Republic of Congo. Despite progress achieved over the past decade in the fight against malaria, further efforts have to be done such as in the surveillance and the containment of Plasmodium falciparum resistant strains. We investigated resistance to artemisinin-based combination therapies currently in use in Democratic Republic of Congo by surveying molecular polymorphisms in three genes: pfcrt, pfmdr1 and pfk13 to explore possible emergence of amodiaquine, lumefantrine or artemisinin resistance in Democratic Republic of Congo...
2017: PloS One
https://www.readbyqxmd.com/read/28591198/single-dose-primaquine-to-reduce-gametocyte-carriage-and-plasmodium-falciparum-transmission-in-cambodia-an-open-label-randomized-trial
#16
Jessica T Lin, Chanthap Lon, Michele D Spring, Somethy Sok, Soklyda Chann, Mali Ittiverakul, Worachet Kuntawunginn, Mok My, Kheangheng Thay, Rifat Rahman, Sujata Balasubramanian, Mengchuor Char, Charlotte A Lanteri, Panita Gosi, Ratawan Ubalee, Steven R Meshnick, David L Saunders
BACKGROUND: Single low dose primaquine (SLD PQ, 0.25mg/kg) is recommended in combination with artemisinin-based combination therapy (ACT) as a gametocytocide to prevent Plasmodium falciparum transmission in areas threatened by artemisinin resistance. To date, no randomized controlled trials have measured primaquine's effect on infectiousness to Anopheline mosquitoes in Southeast Asia. METHODS: Cambodian adults with uncomplicated falciparum malaria were randomized to receive a single 45mg dose of primaquine (equivalent to three SLD PQ) or no primaquine after the third dose of dihydroartemisin-piperaquine (DHP) therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28589330/triple-combination-therapy-and-drug-cycling-tangential-strategies-for-countering-artemisinin-resistance
#17
REVIEW
Bhattacharjee Dipanjan, G Shivaprakash, O Balaji
PURPOSE OF REVIEW: This review attempts to understand the reasons for the successes and failures of the two novel strategies that have slowly begun to emerge as potential counters for anti-malarial drug resistance-"Triple Combination Therapy" and "Drug Cycling." RECENT FINDINGS: Recent reports have suggested that increasing the heterogeneity within the parasite's environment, both at an individual and the population level, may help raise the probabilistic barrier of development of resistance in the parasite...
July 2017: Current Infectious Disease Reports
https://www.readbyqxmd.com/read/28588946/assessing-the-independent-and-combined-effects-of-subsidies-for-antimalarials-and-rapid-diagnostic-testing-on-fever-management-decisions-in-the-retail-sector-results-from-a-factorial-randomised-trial-in-western-kenya
#18
Wendy Prudhomme O'Meara, Manoj Mohanan, Jeremiah Laktabai, Adriane Lesser, Alyssa Platt, Elisa Maffioli, Elizabeth L Turner, Diana Menya
OBJECTIVES: There is an urgent need to understand how to improve targeting of artemisinin combination therapy (ACT) to patients with confirmed malaria infection, including subsidised ACTs sold over-the-counter. We hypothesised that offering an antimalarial subsidy conditional on a positive malaria rapid diagnostic test (RDT) would increase uptake of testing and improve rational use of ACTs. METHODS: We designed a 2×2 factorial randomised experiment evaluating 2 levels of subsidy for RDTs and ACTs...
August 2016: BMJ Global Health
https://www.readbyqxmd.com/read/28583709/imported-malaria-in-pregnant-women-experienced-in-japan
#19
Mikio Kimura, Michiko Koga, Chihiro Hasegawa, Yoshikazu Mutoh, Yasuyuki Kato, Haruhiko Maruyama
INTRODUCTION: With ever-growing global exchanges, the number of travelers, including pregnant women, to the tropics is increasing, which poses a risk of contracting malaria. Although there are several reports on imported malaria in pregnancy from Western countries, those focusing on cases experienced in Japan are very limited. METHODS: We searched for cases of malaria in pregnancy in the treatment records submitted to the Research Group on Chemotherapy of Tropical Diseases, Japan, during the period 1993-2016...
June 2, 2017: Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy
https://www.readbyqxmd.com/read/28580606/combating-multi-drug-resistant-plasmodium-falciparum-malaria
#20
REVIEW
Aung Myint Thu, Aung Pyae Phyo, Jordi Landier, Daniel M Parker, François H Nosten
Over the past 50 years, P. falciparum has developed resistance against all antimalarial drugs used against it: chloroquine, sulphadoxine-pyrimethamine, quinine, piperaquine and mefloquine. More recently, resistance to the artemisinin derivatives and the resulting failure of artemisinin based combination therapy (ACT) are threatening all major gains made in malaria control. Each time resistance has developed over a progression, with delayed clearance of parasites emerging in a few regions, increasing in prevalence and geographic range, and then ultimately resulting in the complete failure of that antimalarial...
June 5, 2017: FEBS Journal
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