What's new for 'Trypanosomatids' in PubMed

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Sent on Saturday, 2009 Nov 21
Search kinetoplastids OR kinetoplastid OR Kinetoplastida OR "trypanosoma brucei" OR leishmania OR brucei OR leishmaniasis OR "African trypanosomiasis"
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PubMed Results

Items 1 -4 of 4

1.	Bioorg Med Chem. 2009 Oct 31. [Epub ahead of print] Synthesis and biological evaluation of trifluralin analogues as antileishmanial agents. Esteves MA, Fragiadaki I, Lopes R, Scoulica E, Cruz ME. Department of Chemical Industry Technologies, INETI, Estrada do Paço do Lumiar, 1649-038 Lisboa, Portugal. A series of new analogues of trifluralin (TFL) were synthesized and characterized in view of changing the unfavorable properties that limits its use as antileishmanial agent. Some of the TFL analogues display more activity than a standard drug (miltefosine) against the promastigote forms of Leishmania infantum and Leishmania donovani and the intracellular form (THP-1 infected with L. infantum). All analogues showed a clear advantage over miltefosine, as they are not hemolytic. Some analogues can conjugate these characteristics with reduced cell toxicity and improved intracellular activity.
	PMID: 19926293 [PubMed - as supplied by publisher]
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2.	Eur J Med Chem. 2009 Nov 6. [Epub ahead of print] Original quinazoline derivatives displaying antiplasmodial properties. Kabri Y, Azas N, Dumètre A, Hutter S, Laget M, Verhaeghe P, Gellis A, Vanelle P. Laboratoire de Pharmacochimie Radicalaire, Faculté de Pharmacie, Universités d'Aix-Marseille I, II et III - UMR CNRS 6264, Laboratoire Chimie Provence, 27 Boulevard Jean Moulin, 13385 Marseille cedex 05, France. The multistep synthesis of new quinazoline-derived molecules and their in vitro antiplasmodial evaluation on the W2 chloroquino-resistant Plasmodium falciparum strain is described herein. These molecules have also been studied concerning their in vitro cytotoxicity toward two human cell lines (K652 and HepG2) in order to calculate their respective selectivity indexes (S.I.). Among the fourteen tested molecules, two exhibited both significant antiplasmodial activity (IC(50)=0.95 and 1.3muM) and low toxicity (IC(50)>100 or 125muM), compared with two reference drugs: chloroquine and doxycycline. The structure activity relationships establish that the molecular scaffold which exerts the best profile is the 6-nitro-2-(tosylmethyl)-N-(3-substituted-phenyl)-quinazolin-4-amine. The hit molecules were finally investigated regarding their potential action toward two other protozoa, Leishmania donovani and Toxoplasma gondii, showing that these molecules display a selective antiplasmodial activity.
	PMID: 19926173 [PubMed - as supplied by publisher]
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3.	Mol Biochem Parasitol. 2009 Nov 16. [Epub ahead of print] Expression of a PTS2truncated hexokinase produces glucose toxicity in Leishmania donovani. Kumar R, Gupta S, Srivastava R, Sahasrabuddhe AA, Gupta CM. Parasitology Division, Central Drug Research Institute, C.S.I.R, Lucknow-226001. Compartmentalization of glycolytic enzymes in glycosomes is vital in trypanosomatid parasites. Retention of these enzymes in the cytosol induces sugar toxicity and accumulation of intermediate metabolites, notably the hexokinase product glucose 6-phosphate. However, the role of hexokinase in sugar mediated toxicity remains unexplored. We have generated Leishmania donovani transfectants expressing a catalytically active cytosolic mutant of hexokinase. In the presence of glucose, these transfectants exhibited toxicity during log and stationary phases of growth. These results suggest that targeting of hexokinase to the glycosome is required to prevent uncontrolled and cytotoxic glucose phosphorylation in L. donovani parasites.
	PMID: 19925831 [PubMed - as supplied by publisher]
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4.	Int J Parasitol. 2009 Nov 16. [Epub ahead of print] Depletion of 14-3-3 proteins in bloodstream-form Trypanosoma brucei inhibits variant surface glycoprotein recycling. Benz C, Engstler M, Hillmer S, Clayton C. Zentrum für Molekulare Biologie der Universität Heidelberg, ZMBH-DKFZ Alliance, Im Neuenheimer Feld 282, D69120 Heidelberg, Germany. Bloodstream-form Trypanosoma brucei have two 14-3-3 proteins, which are required for parasite multiplication. We here describe the effects of 14-3-3 depletion on vesicular transport of variant surface glycoprotein (VSG). 14-3-3 depletion had no detectable effect on de novo synthesis and trafficking of VSG to the cell surface, or on VSG endocytosis. Despite strong inhibition of cell division, the flagellar pocket was not enlarged and the ultrastructure of internal organelles appeared normal. The Rab11-positive recycling endosome compartment was, however, five-fold smaller than normal, and the rate of return of recycling VSG to the surface was correspondingly reduced. Down-regulating 14-3-3 also prevented enlargement of the flagellar pocket by clathrin depletion. These results suggest that there is a remarkably specific requirement for 14-3-3 in normal functioning of the Rab11-positive recycling endosome compartment.
	PMID: 19925803 [PubMed - as supplied by publisher]
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