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Human antiparasitic drugs

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https://www.readbyqxmd.com/read/27865740/sm-p80-based-schistosomiasis-vaccine-preparation-for-human-clinical-trials
#1
REVIEW
Afzal A Siddiqui, Sabrina Z Siddiqui
Mass antiparasitic drug administration programs and other control strategies have made important contributions in reducing the global prevalence of helminths. Schistosomiasis, however, continues to spread to new geographic areas. The advent of a viable vaccine and its deployment, coupled with existing control efforts, is expected to make significant headway towards sustained schistosomiasis control. In 2016, Science ranked the schistosomiasis vaccine as one of the top 10 vaccines that needs to be urgently developed...
November 16, 2016: Trends in Parasitology
https://www.readbyqxmd.com/read/27719626/metabolic-inhibitors-as-antiparasitic-drugs-pharmacological-biochemical-and-molecular-perspectives
#2
Suprabhat Mukherjee, Niladri Mukherjee, Prajna Gayen, Priya Roy, Santi P Sinha Babu
Human diseases caused by the infectious parasites have been one of the major problems throughout the evolutionary journey. Protozoan and metazoan parasitic infections result in a large number of deaths, disabilities and socio-economic loss worldwide to date. Despite our best efforts of developing suitable antiparasitics, these infections take a massive toll on human health. The prevalence of emerging resistance to the existing drugs, lack of efficacy and toxic side effects came out as added complications. Being enlisted under 'neglected' category, serious diseases like leishmaniases, filariases, trypanosomiases etc...
October 4, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27519462/discovery-and-antiparasitic-activity-of-az960-as-a-trypanosoma-brucei-erk8-inhibitor
#3
Ana L Valenciano, Aaron C Ramsey, Webster L Santos, Zachary B Mackey
Human African trypanosomiasis (HAT) is a lethal, vector-borne disease caused by the parasite Trypanosoma brucei. Therapeutic strategies for this neglected tropical disease suffer from disadvantages such as toxicity, high cost, and emerging resistance. Therefore, new drugs with novel modes of action are needed. We screened cultured T. brucei against a focused kinase inhibitor library to identify promising bioactive compounds. Among the ten hits identified from the phenotypic screen, AZ960 emerged as the most promising compound with potent antiparasitic activity (IC50=120nM) and was shown to be a selective inhibitor of an essential gene product, T...
October 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27431220/cryptosporidium-and-toxoplasma-parasites-are-inhibited-by-a-benzoxaborole-targeting-leucyl-trna-synthetase
#4
Andrés Palencia, Ru-Juan Liu, Maria Lukarska, Jiri Gut, Alexandre Bougdour, Bastien Touquet, En-Duo Wang, Xianfeng Li, M R K Alley, Yvonne R Freund, Philip J Rosenthal, Mohamed-Ali Hakimi, Stephen Cusack
The apicomplexan parasites Cryptosporidium and Toxoplasma are serious threats to human health. Cryptosporidiosis is a severe diarrheal disease in malnourished children and immunocompromised individuals, with the only FDA-approved drug treatment currently being nitazoxanide. The existing therapies for toxoplasmosis, an important pathology in immunocompromised individuals and pregnant women, also have serious limitations. With the aim of developing alternative therapeutic options to address these health problems, we tested a number of benzoxaboroles, boron-containing compounds shown to be active against various infectious agents, for inhibition of the growth of Cryptosporidium parasites in mammalian cells...
October 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27297108/pentamidine-blocks-the-interaction-between-mutant-s100a5-and-rage-v-domain-and-inhibits-the-rage-signaling-pathway
#5
Ching Chang Cho, Ruey Hwang Chou, Chin Yu
The human S100 protein family contains small, dimeric and acidic proteins that contain two EF-hand motifs and bind calcium. When S100A5 binds calcium, its conformation changes and promotes interaction with the target protein. The extracellular domain of RAGE (Receptor of Advanced Glycation End products) contain three domains: C1, C2 and V. The RAGE V domain is the target protein of S100A5 that promotes cell survival, growth and differentiation by activating several signaling pathways. Pentamidine is an apoptotic and antiparasitic drug that is used to treat or prevent pneumonia...
August 19, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27236016/nitroimidazole-carboxamides-as-antiparasitic-agents-targeting-giardia-lamblia-entamoeba-histolytica-and-trichomonas-vaginalis
#6
A M Jarrad, A Debnath, Y Miyamoto, K A Hansford, R Pelingon, M S Butler, T Bains, T Karoli, M A T Blaskovich, L Eckmann, M A Cooper
Diarrhoeal diseases caused by the intestinal parasites Giardia lamblia and Entamoeba histolytica constitute a major global health burden. Nitroimidazoles are first-line drugs for the treatment of giardiasis and amebiasis, with metronidazole 1 being the most commonly used drug worldwide. However, treatment failures in giardiasis occur in up to 20% of cases and development of resistance to metronidazole is of concern. We have re-examined 'old' nitroimidazoles as a foundation for the systematic development of next-generation derivatives...
September 14, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27139509/plant-extracts-from-encapsulation-to-application
#7
Brenda Armendáriz-Barragán, Nadiah Zafar, Waisudin Badri, Sergio Arturo Galindo-Rodríguez, Dounia Kabbaj, Hatem Fessi, Abdelhamid Elaissari
INTRODUCTION: Plants are a natural source of various products with diverse biological activities offering treatment for several diseases. Plant extract is a complex mixture of compounds, which can have antioxidant, antibiotic, antiviral, anticancer, antiparasitic, antifungal, hypoglycemic, anti-hypertensive and insecticide properties. The extraction of these extracts requires the use of organic solvents, which not only complicates the formulations but also makes it difficult to directly use the extracts for humans...
August 2016: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/27118499/antimicrobial-antiparasitic-and-anticancer-properties-of-hibiscus-sabdariffa-l-and-its-phytochemicals-in-vitro-and-in-vivo-studies
#8
Sherif T S Hassan, Kateřina Berchová, Miroslava Šudomová
UNLABELLED: In the last few decades, Hibiscus sabdariffa L. (Malvaceae; H. sabdariffa) has gained much attention in research field because of its potentially useful bioactivity as well as a great safety and tolerability. For decades, microbial, parasitic and cancer diseases remain a serious threat to human health and animals as well. To treat such diseases, a search for new sources such as plants that provide various bioactive compounds useful in the treatment of several physiological conditions is urgently needed, since most of the drugs currently used in the therapy have several undesirable side effects, toxicity, and drug resistance...
2016: Ceská a Slovenská Farmacie
https://www.readbyqxmd.com/read/27090120/toxicity-and-potential-utility-of-ivermectin-and-moxidectin-as-xenointoxicants-against-the-common-bed-bug-cimex-lectularius-l
#9
Johnathan M Sheele, Gale E Ridge
The recent resurgence of the common bed bug Cimex lectularius L. throughout western industrialized nations has been facilitated in part by the insect becoming pesticide-resistant. Novel control strategies, including xenointoxication, should be considered to combat C. lectularius. Ivermectin, a U.S. Food and Drug Administration (FDA)-approved treatment for several human parasites, and the antiparasitic drug moxidectin, currently being explored in human clinical trials, were evaluated for efficacy against C. lectularius...
August 2016: Parasitology Research
https://www.readbyqxmd.com/read/27070627/in-vitro-effect-of-the-synthetic-cal14-1a-conotoxin-derived-from-conus-californicus-on-the-human-parasite-toxoplasma-gondii
#10
Marco A De León-Nava, Eunice Romero-Núñez, Angélica Luna-Nophal, Johanna Bernáldez-Sarabia, Liliana N Sánchez-Campos, Alexei F Licea-Navarro, Jorge Morales-Montor, Saé Muñiz-Hernández
Toxins that are secreted by cone snails are small peptides that are used to treat several diseases. However, their effects on parasites with human and veterinary significance are unknown. Toxoplasma gondii is an opportunistic parasite that affects approximately 30% of the world's population and can be lethal in immunologically compromised individuals. The conventional treatment for this parasitic infection has remained the same since the 1950s, and its efficacy is limited to the acute phase of infection. These findings have necessitated the search for new drugs that specifically target T...
April 2016: Marine Drugs
https://www.readbyqxmd.com/read/27045536/closantel-suppresses-angiogenesis-and-cancer-growth-in-zebrafish-models
#11
Xiao-Yu Zhu, Bo Xia, Hong-Cui Liu, Yi-Qiao Xu, Chang-Jiang Huang, Ji-Min Gao, Qiao-Xiang Dong, Chun-Qi Li
Angiogenesis has emerged as an important therapeutic target in several major diseases, including cancer and age-related macular degeneration. The zebrafish offer the potential for high-throughput drug discovery in a whole vertebrate system. In this study, we have taken advantage of the transgenic Tg (fli1a:EGFP) zebrafish line to screen the U.S. Drug Collection Library and identified 11 old drugs with antiangiogenic activity, including Closantel, an FDA-approved broad-spectrum salicylanilide antiparasitic drug for a variety of types of animals...
April 5, 2016: Assay and Drug Development Technologies
https://www.readbyqxmd.com/read/27003405/evaluation-of-medicated-feeds-with-antiparasitical-and-immune-enhanced-chinese-herbal-medicines-against-ichthyophthirius-multifiliis-in-grass-carp-ctenopharyngodon-idellus
#12
De-Jie Lin, Ya-Nan Hua, Qi-Zhong Zhang, De-Hai Xu, Yao-Wu Fu, Yan-Meng Liu, Sheng-Yu Zhou
Since malachite green was banned for using in food fish due to its carcinogenic and teratogenic effects on human, the search of alternative drug to treat Ichthyophthirius multifiliis becomes urgent. This study aimed to (1) evaluate the ethanol extracts of medicinal plants Cynanchum atratum, Zingiber officinale, Cynanchum paniculatum, immunostimulant (A), and immunostimulant (B) for their efficacy against I. multifiliis, and (2) determine effects of medicated feeds with C. atratum, Z. officinale, C. paniculatum, and immunostimulant (A) to treat I...
June 2016: Parasitology Research
https://www.readbyqxmd.com/read/26904134/the-effect-of-aqueous-extract-of-cinnamon-on-the-metabolome-of-plasmodium-falciparum-using-1-hnmr-spectroscopy
#13
Shirin Parvazi, Sedigheh Sadeghi, Mehri Azadi, Maryam Mohammadi, Mohammad Arjmand, Farideh Vahabi, Somye Sadeghzadeh, Zahra Zamani
Malaria is responsible for estimated 584,000 deaths in 2013. Researchers are working on new drugs and medicinal herbs due to drug resistance that is a major problem facing them; the search is on for new medicinal herbs. Cinnamon is the bark of a tree with reported antiparasitic effects. Metabonomics is the simultaneous study of all the metabolites in biological fluids, cells, and tissues detected by high throughput technology. It was decided to determine the mechanism of the effect of aqueous extract of cinnamon on the metabolome of Plasmodium falciparum in vitro using (1)HNMR spectroscopy...
2016: Journal of Tropical Medicine
https://www.readbyqxmd.com/read/26862474/low-dose-benznidazole-treatment-results-in-parasite-clearance-and-attenuates-heart-inflammatory-reaction-in-an-experimental-model-of-infection-with-a-highly-virulent-trypanosoma-cruzi-strain
#14
Ágata Carolina Cevey, Gerardo Ariel Mirkin, Federico Nicolás Penas, Nora Beatriz Goren
Chagas disease, caused by Trypanosoma cruzi, is the main cause of dilated cardiomyopathy in the Americas. Antiparasitic treatment mostly relies on benznidazole (Bzl) due to Nifurtimox shortage or unavailability. Both induce adverse drug effects (ADE) of varied severity in many patients, leading to treatment discontinuation or abandonment. Since dosage may influence ADE, we aimed to assess Bzl efficacy in terms of parasiticidal and anti-inflammatory activity, using doses lower than those previously reported...
April 2016: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/26856301/self-dispersible-nanocrystals-of-albendazole-produced-by-high-pressure-homogenization-and-spray-drying
#15
Alejandro Javier Paredes, Juan Manuel Llabot, Sergio Sánchez Bruni, Daniel Allemandi, Santiago Daniel Palma
Albendazole (ABZ) is a broad-spectrum antiparasitic drug used in the treatment of human or animal infections. Although ABZ has shown a high efficacy for repeated doses in monogastric mammals, its low aqueous solubility leads to erratic bioavailability. The aim of this work was to optimize a procedure in order to obtain ABZ self-dispersible nanocrystals (SDNC) by combining high pressure homogenization (HPH) and spray-drying (SD). The material thus obtained was characterized and the variables affecting both the HPH and SD processes were studied...
October 2016: Drug Development and Industrial Pharmacy
https://www.readbyqxmd.com/read/26824936/killing-of-trypanozoon-parasites-by-the-equine-cathelicidin-ecath1
#16
S Cauchard, N Van Reet, P Büscher, D Goux, J Grötzinger, M Leippe, V Cattoir, C Laugier, J Cauchard
Trypanozoon parasites infect both humans, causing sleeping sickness, and animals, causing nagana, surra, and dourine. Control of nagana and surra depends to a great extent on chemotherapy. However, drug resistance to several of the front-line drugs is rising. Furthermore, there is no official treatment for dourine. Therefore, there is an urgent need to develop antiparasitic agents with novel modes of action. Host defense peptides have recently gained attention as promising candidates. We have previously reported that one such peptide, the equine antimicrobial peptide eCATH1, is highly active against equine Gram-positive and Gram-negative bacteria, without cytotoxicity against mammalian cells at bacteriolytic concentrations...
May 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/26824279/potent-inhibition-of-cyclic-diadenylate-monophosphate-cyclase-by-the-antiparasitic-drug-suramin
#17
Clement Opoku-Temeng, Herman O Sintim
C-di-AMP synthases are essential in several bacteria, including human pathogens; hence these enzymes are potential antibiotic targets. However, there is a dearth of small molecule inhibitors of c-di-AMP metabolism enzymes. Screening of 2000 known drugs against DisA has led to the identification of suramin, an antiparasitic drug as potent inhibitor of c-di-AMP synthase.
March 7, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/26784142/defining-the-targets-of-antiparasitic-compounds
#18
REVIEW
Tina S Skinner-Adams, Subathdrage D M Sumanadasa, Gillian M Fisher, Rohan A Davis, Denise L Doolan, Katherine T Andrews
The treatment of major human parasitic infections is dependent on drugs that are plagued by issues of drug resistance. New chemotherapeutics with novel mechanisms of action (MOA) are desperately needed to combat multi-drug-resistant parasites. Although widespread screening strategies are identifying potential new hits for development against most major human parasitic diseases, in many cases such efforts are hindered by limited MOA data. Although MOA data are not essential for drug development, they can facilitate compound triage and provide a mechanism to combat drug resistance...
May 2016: Drug Discovery Today
https://www.readbyqxmd.com/read/26781029/approaches-for-designing-new-potent-inhibitors-of-farnesyl-pyrophosphate-synthase
#19
REVIEW
Juan B Rodriguez, Bruno N Falcone, Sergio H Szajnman
INTRODUCTION: Farnesyl pyrophosphate synthase (FPPS) catalyzes the condensation of isopentenyl diphosphate with dimethylallyl diphosphate to give rise to one molecule of geranyl diphosphate, which on a further reaction with another molecule of isopentenyl diphosphate forms the 15-carbon isoprenoid farnesyl diphosphate. This molecule is the obliged precursor for the biosynthesis of sterols, ubiquinones, dolichols, heme A, and prenylated proteins. The blockade of FPPS prevents the synthesis of farnesyl diphosphate and the downstream essential products...
2016: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/26699479/dysregulated-yap1-taz-and-tgf-%C3%AE-signaling-mediate-hepatocarcinogenesis-in-mob1a-1b-deficient-mice
#20
Miki Nishio, Keishi Sugimachi, Hiroki Goto, Jia Wang, Takumi Morikawa, Yosuke Miyachi, Yusuke Takano, Hiroki Hikasa, Tohru Itoh, Satoshi O Suzuki, Hiroki Kurihara, Shinichi Aishima, Andrew Leask, Takehiko Sasaki, Toru Nakano, Hiroshi Nishina, Yuji Nishikawa, Yoshitaka Sekido, Kazuwa Nakao, Kazuo Shin-Ya, Koshi Mimori, Akira Suzuki
Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway that coactivate large tumor suppressor homolog (LATS) kinases. Mob1a/1b double deficiency in mouse liver (LMob1DKO) results in hyperplasia of oval cells and immature cholangiocytes accompanied by inflammatory cell infiltration and fibrosis. More than half of mutant mice die within 3 wk of birth. All survivors eventually develop liver cancers, particularly combined hepatocellular and cholangiocarcinomas (cHC-CCs) and intrahepatic cholangiocellular carcinomas (ICCs), and die by age 60 wk...
January 5, 2016: Proceedings of the National Academy of Sciences of the United States of America
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