International Journal for Parasitology: Drugs and Drug Resistance This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Screening of a PDE-focused library identifies imidazoles with in vitro and in vivo antischistosomal activity
We report the evaluation of 265 compounds from a PDE-focused library for their antischistosomal activity, assessed in vitro using Schistosoma mansoni. Of the tested compounds, 171 (64%) displayed selective in vitro activity, with 16 causing worm hypermotility/spastic contractions and 41 inducing various degrees of worm killing at 100 μM, with the surviving worms displaying sluggish movement, worm unpairing and complete absence of eggs. The compounds that did not affect worm viability (n = 72) induced a complete cessation of ovipositing. 82% of the compounds had an impact on male worms whereas female worms were barel...
Source: International Journal for Parasitology: Drugs and Drug Resistance - January 15, 2019 Category: Parasitology Source Type: research

Selected α-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro
Publication date: Available online 4 January 2019Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): H.M.P. Dilrukshi Herath, Sarah Preston, Abdul Jabbar, Jose Garcia-Bustos, Russell S. Addison, Sasha Hayes, Topul Rali, Tao Wang, Anson V. Koehler, Bill C.H. Chang, Andreas Hofmann, Rohan A. Davis, Robin B. GasserAbstractDue to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has...
Source: International Journal for Parasitology: Drugs and Drug Resistance - January 5, 2019 Category: Parasitology Source Type: research

Tetrahydroquinoxalines induce a lethal evisceration phenotype in Haemonchus contortus in vitro
Publication date: Available online 30 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Yaqing Jiao, Sarah Preston, Jose F. Garcia-Bustos, Jonathan B. Baell, Sabatino Ventura, Thuy Le, Nicole McNamara, Nghi Nguyen, Antony Botteon, Cameron Skinner, Jill Danne, Sarah Ellis, Anson V. Koehler, Tao Wang, Bill C.H. Chang, Andreas Hofmann, Abdul Jabbar, Robin B. GasserAbstractIn the present study, the anthelmintic activity of a human tyrosine kinase inhibitor, AG-1295, and 14 related tetrahydroquinoxaline analogues against Haemonchus contortus was explored. These compounds were scree...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 30, 2018 Category: Parasitology Source Type: research

Menthol acts as a positive allosteric modulator on nematode levamisole sensitive nicotinic acetylcholine receptors
In this study we examined the effects of monoterpenoid compounds on a levamisole sensitive nAChR from Oesophagostomum dentatum and a nicotine sensitive nAChR from Ascaris suum. We expressed the receptors in Xenopus laevis oocytes and used two-electrode voltage-clamp to characterize the effect of various compounds on these cys-loop receptors. At 100 μM the majority of these compounds acted as antagonists. Interestingly, further experiments revealed that both 0.1 μM and 10 μM menthol potentiated acetylcholine and levamisole responses in the levamisole sensitive receptor but not the nicotine sensitive receptor. We al...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 30, 2018 Category: Parasitology Source Type: research

New life for an old drug: In vitro and in vivo effects of the anthelmintic drug niclosamide against Toxoplasma gondii RH strain
In conclusion, our results support the efficacy of niclosamide as a potential compound for the treatment of T. gondii infection.Graphical abstract (Source: International Journal for Parasitology: Drugs and Drug Resistance)
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 21, 2018 Category: Parasitology Source Type: research

Transient temperature fluctuations severely decrease P. falciparum susceptibility to artemisinin in vitro
We examined the impact of short pulses of low temperature on ring-stage susceptibility of Plasmodium falciparum to artemisinin in vitro. The usually artemisinin-sensitive clone 3D7 exhibited substantially reduced ring-stage susceptibility to a 4-h pulse of 700 nM dihydro-artemisinin administered during a 5-h pulse of low temperature down to 17 °C. Parasite growth through the subsequent asexual cycle was not affected by the temperature pulse. Chloroquine and pyronaridine susceptibility, in a standard 48-h test, was not affected by brief exposures to low temperature. Fever-like temperature pulses up to 40 °C were als...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 16, 2018 Category: Parasitology Source Type: research

Ascorbic acid reduces the genetic damage caused by miltefosine (hexadecylphosphocholine) in animals infected by Leishmania (Leishamnia) infantum without decreasing its antileishmanial activity
Publication date: Available online 13 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Patrícia Valéria Castelo-Branco, Hugo José Alves, Raissa Lacerda Pontes, Vera Lucia Maciel-Silva, Silma Regina Ferreira PereiraAbstractLeishamaniasis is a neglected disease caused by over 20 Leishmania species, occurring in more than a hundred countries. Miltefosine (hexadecylphosphocholine) is the single oral drug used in treatment for leshmaniases, including cases of infections resistant to pentavalent antimony. Our group has recently demonstrated the ability of miltefosine to cause ge...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 14, 2018 Category: Parasitology Source Type: research

Immunosuppression of Syrian golden hamsters accelerates relapse but not the emergence of resistance in Leishmania infantum following recurrent miltefosine pressure
This study evaluated the effect of immunosuppression (cyclophosphamide 150 mg/kg once weekly) on the development of MIL-resistance in Syrian golden hamsters infected with Leishmania infantum. The hamsters were treated with MIL (20 mg/kg orally for 5 days) whenever clinical signs of infection or relapse were observed. The immunosuppression resulted in a significant depletion of CD4+ lymphocytes and MHCII-expressing cells in peripheral blood, and a concomitant increase in tissue parasite burdens and shorter time to relapse, but the strain's susceptibility upon repeated MIL exposure remained unaltered. This study demonstr...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 11, 2018 Category: Parasitology Source Type: research

Overexpression of plasmepsin II and plasmepsin III does not directly cause reduction in Plasmodium falciparum sensitivity to artesunate, chloroquine and piperaquine
Publication date: Available online 1 December 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Duangkamon Loesbanluechai, Namfon Kotanan, Cristina de Cozar, Theerarat Kochakarn, Megan R. Ansbro, Kesinee Chotivanich, Nicholas J. White, Prapon Wilairat, Marcus C.S. Lee, Francisco Javier Gamo, Laura Maria Sanz, Thanat Chookajorn, Krittikorn KümpornsinAbstractArtemisinin derivatives and their partner drugs in artemisinin combination therapies (ACTs) have played a pivotal role in global malaria mortality reduction during the last two decades. The loss of artemisinin efficacy due to evolvi...
Source: International Journal for Parasitology: Drugs and Drug Resistance - December 2, 2018 Category: Parasitology Source Type: research

Nicotine-sensitive acetylcholine receptors are relevant pharmacological targets for the control of multidrug resistant parasitic nematodes
Publication date: Available online 20 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Claude L. Charvet, Fabrice Guégnard, Elise Courtot, Jacques Cortet, Cedric NeveuAbstractThe control of parasitic nematodes impacting animal health relies on the use of broad spectrum anthelmintics. However, intensive use of these drugs has led to the selection of resistant parasites in livestock industry. In that respect, there is currently an urgent need for novel compounds able to control resistant parasites. Nicotine has also historically been used as a de-wormer but was removed from th...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 21, 2018 Category: Parasitology Source Type: research

TPT sulfonate, a single, oral dose schistosomicidal prodrug: In vivo efficacy, disposition and metabolic profiling
Publication date: Available online 20 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Alan R. Wolfe, R. Jeffrey Neitz, Mark Burlingame, Brian M. Suzuki, K.C. Lim, Mark Scheideler, David L. Nelson, Leslie Z. Benet, Conor R. CaffreyAbstractTreatment of schistosomiasis relies precariously on just one drug, praziquantel (PZQ). In the search for alternatives, 15 S-[2-(alkylamino)alkane] thiosulfuric acids were obtained from a previous research program and profiled in mice for efficacy against both mature (>42-day-old) and juvenile (21-day-old) Schistosoma mansoni using a screen...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 21, 2018 Category: Parasitology Source Type: research

Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni
Publication date: Available online 13 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Gilda Padalino, Salvatore Ferla, Andrea Brancale, Iain W. Chalmers, Karl F. HoffmannAbstractSchistosomiasis endangers the lives of greater than 200 million people every year and is predominantly controlled by a single class chemotherapy, praziquantel (PZQ). Development of PZQ replacement (to combat the threat of PZQ insensitivity/resistance arising) or combinatorial (to facilitate the killing of PZQ-insensitive juvenile schistosomes) chemotherapies would help sustain this control strategy i...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 14, 2018 Category: Parasitology Source Type: research

Derivatives of a benzoquinone acyl hydrazone with activity against Toxoplasma gondii
Publication date: Available online 10 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): A.G. Sanford, T.T. Schulze, L.P. Potluri, G.F. Watson, E.B. Darner, S.J. Zach, R.M. Hemsley, A.I. Wallick, R.C. Warner, S.A. Charman, X. Wang, J.L. Vennerstrom, P.H. DavisAbstractToxoplasma gondii is an obligate intracellular parasite with global incidence. The acute infection, toxoplasmosis, is treatable but current regimens have poor host tolerance and no cure has been found for latent infections. This work builds upon a previous high throughput screen which identified benzoquinone acyl h...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 11, 2018 Category: Parasitology Source Type: research

An Abies procera-derived tetracyclic triterpene containing a steroid-like nucleus core and a lactone side chain attenuates in vitro survival of both Fasciola hepatica and Schistosoma mansoni
Publication date: December 2018Source: International Journal for Parasitology: Drugs and Drug Resistance, Volume 8, Issue 3Author(s): Helen L. Whiteland, Anand Chakroborty, Josephine E. Forde-Thomas, Alessandra Crusco, Alan Cookson, Jackie Hollinshead, Caroline A. Fenn, Barbara Bartholomew, Peter A. Holdsworth, Maggie Fisher, Robert J. Nash, Karl F. HoffmannAbstractTwo economically and biomedically important platyhelminth species, Fasciola hepatica (liver fluke) and Schistosoma mansoni (blood fluke), are responsible for the neglected tropical diseases (NTDs) fasciolosis and schistosomiasis. Due to the absence of prophylact...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 11, 2018 Category: Parasitology Source Type: research

Anthelmintics – from Discovery to Resistance III (Indian Rocks Beach, FL, 2018)
Publication date: Available online 5 November 2018Source: International Journal for Parasitology: Drugs and Drug ResistanceAuthor(s): Adrian J. Wolstenholme, Richard J. MartinAbstractThe third scientific meeting in the series “Anthelmintics: From Discovery to Resistance” was held in Indian Rocks Beach, Florida, at the end of January 2018. The meeting focused on a variety of topics related to the title, including the identification of novel targets and new leads, the mechanism of action of existing drugs and the genetic basis of resistance against them. Throughout there was an emphasis on the exploitation of new technol...
Source: International Journal for Parasitology: Drugs and Drug Resistance - November 6, 2018 Category: Parasitology Source Type: research