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https://www.readbyqxmd.com/read/29345221/therapeutic-response-to-dihydroartemisinin-piperaquine-for-p-falciparum-and-p-vivax-nine-years-after-its-introduction-in-southern-papua-indonesia
#1
Jeanne Rini Poespoprodjo, Enny Kenangalem, Johny Wafom, Freis Chandrawati, Agatha M Puspitasari, Benedikt Ley, Leily Trianti, Zoé Korten, Asik Surya, Din Syafruddin, Nicholas M Anstey, Jutta Marfurt, Rintis Noviyanti, Ric N Price
Dihydroartemisinin-piperaquine (DHP) has been the first-line treatment of uncomplicated malaria due to both Plasmodium falciparum and Plasmodium vivax infections in Papua, Indonesia, since March 2006. The efficacy of DHP was reassessed to determine whether there had been any decline following almost a decade of its extensive use. An open-label drug efficacy study of DHP for uncomplicated P. falciparum and P. vivax malaria was carried out between March 2015 and April 2016 in Timika, Papua, Indonesia. Patients with uncomplicated malaria were administered supervised DHP tablets once daily for 3 days...
January 15, 2018: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29342187/induction-of-high-tolerance-to-artemisinin-by-sub-lethal-administration-a-new-in-vitro-model-of-p-falciparum
#2
Serena De Lucia, Ioannis Tsamesidis, Maria Carmina Pau, Kristina R Kesely, Antonella Pantaleo, Francesco Turrini
Artemisinin resistance is a major threat to malaria control efforts. Resistance is characterized by an increase in the Plasmodium falciparum parasite clearance half-life following treatment with artemisinin-based combination therapies (ACTs) and an increase in the percentage of surviving parasites. The remarkably short blood half-life of artemisinin derivatives may contribute to drug-resistance, possibly through factors including sub-lethal plasma concentrations and inadequate exposure. Here we selected for a new strain of artemisinin resistant parasites, termed the artemisinin resistant strain 1 (ARS1), by treating P...
2018: PloS One
https://www.readbyqxmd.com/read/29337533/localized-fe-ii-induced-cytotoxic-reactive-oxygen-species-generating-nano-system-for-enhanced-anticancer-therapy
#3
Yuxue Ding, Jiaxun Wan, Zihao Zhang, Fang Wang, Jia Guo, Changchun Wang
The anticancer therapy on basis of reactive oxygen species (ROS)-mediated cellular apoptosis has achieved great progress. However, this kind of theraputic strategy still faces some challenges such as light, photosensitizer and oxygen (O2) dependence. In this article, a ROS-mediated anticancer therapy independent of light, photosensitizer and oxygen was established based on a Fe2+-induced ROS-generating nano-system. First, artemisinin (ART) was loaded in porous magnetic supraparticles (MSP) by a nano-deposition method...
January 16, 2018: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/29334942/poor-response-to-artesunate-treatment-in-two-patients-with-severe-malaria-on-the-thai-myanmar-border
#4
Aung Pyae Phyo, Kyaw Kyaw Win, Aung Myint Thu, Lei Lei Swe, Htike Htike, Candy Beau, Kanlaya Sriprawat, Markus Winterberg, Stephane Proux, Mallika Imwong, Elizabeth A Ashley, Francois Nosten
BACKGROUND: Malaria has declined dramatically along the Thai-Myanmar border in recent years due to malaria control and elimination programmes. However, at the same time, artemisinin resistance has spread, raising concerns about the efficacy of parenteral artesunate for the treatment of severe malaria. CASE PRESENTATION: In November 2015 and April 2017, two patients were treated for severe malaria with parenteral artesunate. Quinine was added within 24 h due to an initial poor response to treatment...
January 15, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29326018/semisynthesis-cytotoxicity-antimalarial-evaluation-and-structure-activity-relationship-of-two-series-of-triterpene-derivatives
#5
Simone Tasca Cargnin, Andressa Finkler Staudt, Patrícia Medeiros, Daniel de Medeiros Sol Sol, Ana Paula de Azevedo Dos Santos, Fernando Berton Zanchi, Grace Gosmann, Antonio Puyet, Carolina Bioni Garcia Teles, Simone Baggio Gnoatto
In this report, we describe the semisynthesis of two series of ursolic and betulinic acid derivatives through designed by modifications at the C-3 and C-28 positions and demonstrate their antimalarial activity against chloroquine-resistant P. falciparum (W2 strain). Structural modifications at C-3 were more advantageous to antimalarial activity than simultaneous modifications at C-3 and C-28 positions. The ester derivative, 3β-butanoyl betulinic acid (7b), was the most active compound (IC50 = 3.4 µM) and it did not exhibit cytotoxicity against VERO nor HepG2 cells (CC50 > 400 µM), showing selectivity towards parasites (selectivity index > 117...
December 29, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29325068/emergence-of-non-falciparum-plasmodium-infection-despite-regular-artemisinin-combination-therapy-in-a-18-month-longitudinal-study-of-ugandan-children-and-their-mothers
#6
Martha Betson, Sarah Clifford, Michelle Stanton, Narcis B Kabatereine, J Russell Stothard
As part of a longitudinal cohort investigation of intestinal schistosomiasis and malaria in Ugandan children and their mothers on the shorelines of Lakes Victoria and Albert, we documented risk factors and morbidity associated with non-falciparum Plasmodium infections and the longitudinal dynamics of Plasmodium species in children. Host age, household location and P. falciparum infection were strongly associated with non-falciparum Plasmodium infections, and P. malariae infection was associated with splenomegaly...
January 6, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29324864/safety-of-single-low-dose-primaquine-in-glucose-6-phosphate-dehydrogenase-deficient-falciparum-infected-african-males-two-open-label-randomized-safety-trials
#7
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
https://www.readbyqxmd.com/read/29324251/potential-role-of-plasmodium-falciparum-exported-protein-1-in-the-chloroquine-mode-of-action
#8
Andreas Martin Lisewski, Joel Patrick Quiros, Monica Mittal, Nagireddy Putluri, Arun Sreekumar, Jesper Z Haeggström, Olivier Lichtarge
In the human malaria parasite Plasmodium falciparum, membrane glutathione S-transferases (GST) have recently emerged as potential cellular detoxifying units and as drug target candidates with the artemisinin (ART) class of antimalarials inhibiting their activity at single-digit nanomolar potency when activated by iron sources such as cytotoxic hematin. Here we put forward the hypothesis that the membrane GST Plasmodium falciparum exported protein 1 (PfEXP1, PF3D7_1121600) might be directly involved in the mode of action of the unrelated antimalarial 4-aminoquinoline drug chloroquine (CQ)...
December 27, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/29323895/computer-assisted-3d-structure-elucidation-case-3d-of-natural-products-combining-isotropic-and-anisotropic-nmr-parameters
#9
Armando Navarro-Vázquez, Roberto R Gil, Kirill Blinov
A computer-assisted structural elucidation (CASE-3D) strategy based on the use of isotropic and/or anisotropic NMR data is proposed to elucidate relative configuration and preferred conformation in complex natural products. The methodology involves the selection of conformational models through the use of the Akaike Information Criterion and scoring of the different configurations. As illustrative examples, the methodology furnished the correct configuration of the already known compounds artemisinin (1) and homodimericin A (2)...
January 11, 2018: Journal of Natural Products
https://www.readbyqxmd.com/read/29323879/malaria-derived-gpi-anchor-enhances-anti-pfs25-functional-antibodies-that-block-malaria-transmission
#10
Neeraj Kapoor, Ivana Vanjak, James Rozzelle, Aym Berges, Wei Chan, Gang Yin, Cuong Tran, Aaron K Sato, Alexander R Steiner, Thao P Pham, Ashley J Birkett, Carole Long, Jeff Fairman, Kazutoyo Miura
Malaria, one of the most common vector borne human diseas-es, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429,000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts towards development of vaccines to prevent transmission are still needed. Pfs25, a post-fertilization stage parasite surface antigen, is a leading transmission-blocking vaccine (TBV) candidate. It is postulated that Pfs25 anchors to the cell membrane using a glycosylphosphatidyl-inositol (GPI) linker, which itself possesses proinflammatory properties...
January 11, 2018: Biochemistry
https://www.readbyqxmd.com/read/29320822/antimalarial-activity-of-c-10-substituted-triazolyl-artemisinin
#11
Gab-Man Park, Hyun Park, Sangtae Oh, Seokjoon Lee
We synthesized C-10 substituted triazolyl artemisinins by the Huisgen cycloaddition reaction between dihydroartemisinins (2) and variously substituted 1, 2, 3-triazoles (8a-8h). The antimalarial activities of 32 novel artemisinin derivatives were screened against a chloroquine-resistant parasite. Among them, triazolyl artemisinins with electron-withdrawing groups showed stronger antimalarial activities than those shown by the derivatives having electron-donating groups. In particularly, m-chlorotriazolyl artemisinin (9d-12d) showed antimalarial activity equivalent to that of artemisinin and could be a strong drug candidate...
December 2017: Korean Journal of Parasitology
https://www.readbyqxmd.com/read/29320160/efforts-aimed-to-reduce-attrition-in-antimalarial-drug-discovery-a-systematic-evaluation-of-current-antimalarial-targets-portfolio
#12
María Jesus Chaparro, Felix Calderon, Pablo Castañeda, Elena Fernandez Alvaro, Raquel Gabarro, Francisco-Javier Gamo, María G Gómez-Lorenzo, Julio Martín, Esther Fernandez
Malaria remains a major global health problem. In 2015 alone, more than 200 million cases of malaria were reported, and more than 400,000 deaths occurred. Since 2010, emerging resistance to current front-line ACTs (Artemisinin Combination Therapies) has been detected in endemic countries. Therefore, there is an urgency for new therapies based on novel modes of action, able to relieve symptoms as fast as the artemisinins and/or block malaria transmission. During the past few years, the antimalarial community has focused their efforts on phenotypic screening as a pragmatic approach to identify new hits...
January 10, 2018: ACS Infectious Diseases
https://www.readbyqxmd.com/read/29318819/-analysis-of-spatial-distribution-of-artemisinin-in-artemisia-annua-in-china
#13
Xiao-Bo Zhang, Lan-Ping Guo, Zhi-Dong Qiu, Xiao-Bo Qu, Hui Wang, Zhi-Xian Jing, Lu-Qi Huang
Geo-herbals are preferred by long-term clinical application of Chinese medicine, they are produced in a specific area and affected by the specific production and processing methods. Geo-herbals have a high reputation, compared with other regions produced by the same kind of herbs with good quality, efficacy and stable quality characteristics. Geo-herbal is a unique concept that has been formed by the history of Chinese civilization for thousands of years and the history of Chinese medicine. According to the definition of geo-herbal, it can be seen that there are some differences in the quality and efficacy of the same kind of medicinal herbs in different regions, and there is some similarity in the specific area...
November 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29317166/synthesis-in-vitro-antimalarial-activities-and-cytotoxicities-of-amino-artemisinin-ferrocene-derivatives
#14
Christo de Lange, Dina Coertzen, Frans J Smit, Johannes F Wentzel, Ho Ning Wong, Lyn-Marie Birkholtz, Richard K Haynes, David D N'Da
Novel derivatives bearing a ferrocene attached via a piperazine linker to C-10 of the artemisinin nucleus were prepared from dihydroartemisinin and screened against chloroquine (CQ) sensitive NF54 and CQ resistant K1 and W2 strains of Plasmodium falciparum (Pf) parasites. The overall aim is to imprint oxidant (from the artemisinin) and redox (from the ferrocene) activities. In a preliminary assessment, these compounds were shown to possess activities in the low nM range with the most active being compound 6 with IC50 values of 2...
December 26, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29315234/curcumin-artemisinin-coamorphous-solid-xenograft-model-preclinical-study
#15
M K Chaitanya Mannava, Kuthuru Suresh, Manish Kumar Bommaka, Durga Bhavani Konga, Ashwini Nangia
Curcumin is a natural compound present in Indian spice turmeric. It has diverse pharmacological action but low oral solubility and bioavailability continue to limit its use as a drug. With the aim of improving the bioavailability of Curcumin (CUR), we evaluated Curcumin-Pyrogallol (CUR-PYR) cocrystal and Curcumin-Artemisinin (CUR-ART) coamorphous solid. Both of these solid forms exhibited superior dissolution and pharmacokinetic behavior compared to pure CUR, which is practically insoluble in water. CUR-ART coamorphous solid showed two fold higher bioavailability than CUR-PYR cocrystal (at 200 mg/kg oral dose)...
January 9, 2018: Pharmaceutics
https://www.readbyqxmd.com/read/29311435/preparative-separation-of-high-purity-dihydroartemisinic-acid-from-artemisinin-production-waste-by-combined-chromatography
#16
Shuoqian Liu, Jorge Freire da Silva Ferreira, Dongming Tian, Yuwei Tang, Liping Liu, Wei Yang, Zhonghua Liu, Na Tian
In order to make full use of artemisinin production waste and thus to reduce the production cost of artemisinin, we developed an efficient and scalable method to isolate high-purity dihydroartemisinic acid from artemisinin production waste by combining anion-exchange resin with silica-gel column chromatography. The adsorption and desorption characteristics of dihydroartemisinic acid on 10 types of anion-exchange resin were investigated, and the results showed that the 717 anion-exchange resin exhibited the highest capacity of adsorption and desorption to dihydroartemisinic acid...
December 28, 2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29310655/methylene-blue-induced-morphological-deformations-in-plasmodium-falciparum-gametocytes-implications-for-transmission-blocking
#17
Ishan Wadi, C Radhakrishna Pillai, Anupkumar R Anvikar, Abhinav Sinha, Mahendra Nath, Neena Valecha
BACKGROUND: Malaria remains a global health problem despite availability of effective tools. For malaria elimination, drugs targeting sexual stages of Plasmodium falciparum need to be incorporated in treatment regimen along with schizonticidal drugs to interrupt transmission. Primaquine is recommended as a transmission blocking drug for its effect on mature gametocytes but is not extensively utilized because of associated safety concerns among glucose-6-phosphate dehydrogenase (G6PD) deficient patients...
January 8, 2018: Malaria Journal
https://www.readbyqxmd.com/read/29309768/toxicity-and-related-mechanisms-of-dihydroartemisinin-on-porcine-oocyte-maturation-in-vitro
#18
Yan Luo, Man-Ju Che, Cong Liu, Hua-Ge Liu, Xiang-Wei Fu, Yun-Peng Hou
Dihydroartemisinin (DHA), the main active metabolite of artemisinin, has been used to treat malaria and has anticancer activities. Previous work has shown that DHA has negative impacts on embryos in rodents and primates. However, whether DHA has adverse effects on oocyte maturation is unknown. In the present study, we evaluated the toxic effects and possible mechanisms of DHA on porcine oocyte maturation. The results showed that exposure to DHA inhibited porcine oocyte polar body extrusion, and blocked cell cycle progression...
January 5, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29305894/beyond-malaria-the-inhibition-of-viruses-by-artemisinin-type-compounds
#19
REVIEW
Thomas Efferth
No abstract text is available yet for this article.
January 3, 2018: Biotechnology Advances
https://www.readbyqxmd.com/read/29301383/increasing-the-strength-and-production-of-artemisinin-and-its-derivatives
#20
REVIEW
Syed Lal Badshah, Asad Ullah, Nasir Ahmad, Zainab M Almarhoon, Yahia Mabkhot
Artemisinin is a natural sesquiterpene lactone obtained from the Artemisia annua herb. It is widely used for the treatment of malaria. In this article, we have reviewed the role of artemisinin in controlling malaria, spread of resistance to artemisinin and the different methods used for its large scale production. The highest amount of artemisinin gene expression in tobacco leaf chloroplast leads to the production of 0.8 mg/g of the dry weight of the plant. This will revolutionize the treatment and control of malaria in third world countries...
January 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
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