What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2010 Aug 18
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 - 8 of 8

1.	Mar Drugs. 2010 Jul 14;8(7):2162-74. Bromopyrrole Alkaloids as Lead Compounds against Protozoan Parasites. Scala F, Fattorusso E, Menna M, Taglialatela-Scafati O, Tierney M, Kaiser M, Tasdemir D. Dipartimento di Chimica delle Sostanze Naturali, Università di Napoli "Federico II", Via D. Montesano, 49, I-80131, Napoli, Italy; E-Mails: fernando.scala@unina.it (F.S.); fattoru@unina.it (E.F.); mlmenna@unina.it (M.M.). Abstract In the present study, 13 bromopyrrole alkaloids, including the oroidin analogs hymenidin (2), dispacamide B (3) and dispacamide D (4), stevensine (5) and spongiacidin B (6), their derivatives lacking the imidazole ring bromoaldisin (7), longamide B (8) and longamide A (9), the dimeric oroidin derivatives sceptrin (10) and dibromopalau'amine (11), and the non-oroidin bromopyrrolohomoarginin (12), manzacidin A (13), and agelongine (14), obtained from marine sponges belonging to Axinella and Agelas genera have been screened in vitro against four parasitic protozoa, i.e., two Trypanosoma species (T. brucei rhodesiense and T. cruzi), Leishmania donovani and Plasmodium falciparum (K1 strain, a chloroquine resistant strain), responsible of human diseases with high morbidity and, in the case of malaria, high mortality. Our results indicate longamide B (8) and dibromopalau'amine (11) to be promising trypanocidal and antileishmanial agents, while dispacamide B (3) and spongiacidin B (6) emerge as antimalarial lead compounds. In addition, evaluation of the activity of the test alkaloids (2-14) against three different enzymes (PfFabI, PfFabG, PfFabZ) involved in the de novo fatty acid biosynthesis pathway of P. falciparum (PfFAS-II) identified bromopyrrolohomoarginin (12) as a potent inhibitor of PfFabZ. The structural similarity within the series of tested molecules allowed us to draw some preliminary structure-activity relationships. Tests against the mammalian L6 cells revealed important clues on therapeutic index of the metabolites. This is the first detailed study on the antiprotozoal potential of marine bromopyrrole alkaloids.
	PMID: 20714430 [PubMed - in process]
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2.	PLoS Pathog. 2010 Aug 12;6(8). pii: e1001045. Tip-DC Development during Parasitic Infection Is Regulated by IL-10 and Requires CCL2/CCR2, IFN-gamma and MyD88 Signaling. Bosschaerts T, Guilliams M, Stijlemans B, Morias Y, Engel D, Tacke F, Hérin M, De Baetselier P, Beschin A. Department of Molecular and Cellular Interactions, VIB, Brussels, Belgium. Abstract The development of classically activated monocytic cells (M1) is a prerequisite for effective elimination of parasites, including African trypanosomes. However, persistent activation of M1 that produce pathogenic molecules such as TNF and NO contributes to the development of trypanosome infection-associated tissue injury including liver cell necrosis in experimental mouse models. Aiming to identify mechanisms involved in regulation of M1 activity, we have recently documented that during Trypanosoma brucei infection, CD11b(+)Ly6C(+)CD11c(+) TNF and iNOS producing DCs (Tip-DCs) represent the major pathogenic M1 liver subpopulation. By using gene expression analyses, KO mice and cytokine neutralizing antibodies, we show here that the conversion of CD11b(+)Ly6C(+) monocytic cells to pathogenic Tip-DCs in the liver of T. brucei infected mice consists of a three-step process including (i) a CCR2-dependent but CCR5- and Mif-independent step crucial for emigration of CD11b(+)Ly6C(+) monocytic cells from the bone marrow but dispensable for their blood to liver migration; (ii) a differentiation step of liver CD11b(+)Ly6C(+) monocytic cells to immature inflammatory DCs (CD11c(+) but CD80/CD86/MHC-II(low)) which is IFN-gamma and MyD88 signaling independent; and (iii) a maturation step of inflammatory DCs to functional (CD80/CD86/MHC-II(high)) TNF and NO producing Tip-DCs which is IFN-gamma and MyD88 signaling dependent. Moreover, IL-10 could limit CCR2-mediated egression of CD11b(+)Ly6C(+) monocytic cells from the bone marrow by limiting Ccl2 expression by liver monocytic cells, as well as their differentiation and maturation to Tip-DCs in the liver, showing that IL-10 works at multiple levels to dampen Tip-DC mediated pathogenicity during T. brucei infection. A wide spectrum of liver diseases associates with alteration of monocyte recruitment, phenotype or function, which could be modulated by IL-10. Therefore, investigating the contribution of recruited monocytes to African trypanosome induced liver injury could potentially identify new targets to treat hepatic inflammation in general, and during parasite infection in particular.
	PMID: 20714353 [PubMed - in process]
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3.	Molecules. 2010 Aug 9;15(8):5408-22. Using Topological Indices to Predict Anti-Alzheimer and Anti-Parasitic GSK-3 Inhibitors by Multi-Target QSAR in Silico Screening. García I, Fall Y, Gómez G. Department of Organic Chemistry, Faculty of Chemistry, University of Vigo, Spain. iselapintos@yahoo.es. Abstract Plasmodium falciparum, Leishmania, Trypanosomes, are the causers of diseases such as malaria, leishmaniasis and African trypanosomiasis that nowadays are the most serious parasitic health problems worldwide. The great number of deaths and the few drugs available against these parasites, make necessary the search for new drugs. Some of these antiparasitic drugs also are GSK-3 inhibitors. GSKI-3 are candidates to develop drugs for the treatment of Alzheimer's disease. In this work topological descriptors for a large series of 3,370 active/non-active compounds were initially calculated with the ModesLab software. Linear Discriminant Analysis was used to fit the classification function and it predicts heterogeneous series of compounds like paullones, indirubins, meridians, etc. This study thus provided a general evaluation of these types of molecules.
	PMID: 20714305 [PubMed - in process]
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4.	Antimicrob Agents Chemother. 2010 Aug 16. [Epub ahead of print] Reduction in skin/systemic parasite burdens as a combined effect of topical paromomycin and oral miltefosine treatment of mice experimentally infected with Leishmania (Leishmania) amazonensis.Aguiar MG, Pereira AM, Fernandes AP, Ferreira LA. Department of Pharmaceutics; Department of Clinical and Toxicological Analysis, Faculty of Pharmacy, Federal University Minas Gerais, Av Antônio Carlos, 6627, Belo Horizonte, Brazil; Newton Paiva University Center, Belo Horizonte, Brazil. Abstract This study aimed to investigate the activity of the combination of topical paromomycin gel and oral miltefosine for the treatment of experimental cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis. The efficacy of the combination, evaluated by measuring lesion size and parasite burden in the skin and spleen, was assessed in BALB/c mice infected by Leishmania (L.) amazonensis. The miltefosine was administered orally at 10 mg/kg/day for 10 days, while 10% paromomycin gel was applied topically twice a day for 20 days. Treatment of the experimentally infected animals with topical paromomycin + oral miltefosine combination induced a statistically significant reduction in lesion size and parasite burden in the skin and spleen, with complete healing of ulcers, as compared with those treated with placebo group. Combination of topical paromomycin gel + oral miltefosine provides an enhanced efficacy in the treatment of L. (L.) amazonensis-infected mice, thus presenting a higher activity than that observed for the monotherapeutic regimens.
	PMID: 20713665 [PubMed - as supplied by publisher]
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5.	Exp Parasitol. 2010 Aug 13. [Epub ahead of print] Leishmania amazonensis META2 protein confers protection against heat shock and oxidative stress. Ramos CS , Yokoyama-Yasunaka JK, Giraldez CG, Price HP, Mortara RA, Smith DF, Uliana SR. Departamento de Parasitologia, Instituto de Ciências Biomédicas,Universidade de São Paulo, USP, São Paulo, SP, Brazil. Abstract The META cluster of Leishmania amazonensis contains both META1 and META2 genes, which are upregulated in metacyclic promastigotes and encode proteins containing the META domain. Previous studies defined META2 as a 48.0 kDa protein, which is conserved in other Leishmania species and in Trypanosoma brucei. In this work we demonstrate that META2 protein expression is regulated during the Leishmania life cycle but constitutive in T. brucei. META2 protein is present in the cytoplasm and flagellum of L. amazonensis promastigotes. Leishmania META2 null replacement mutants are more sensitive to oxidative stress and, upon heat shock, assume rounded morphology with shortened flagella. The increased susceptibility of null parasites to heat shock is reversed by extra-chromosomal expression of the META2 gene. Defective Leishmania promastigotes exhibit decreased ability to survive in macrophages. In contrast, META2 expression is decreased by 80% in RNAi induced T. brucei procyclics with no measurable effect on survival or resistance to heat shock.
	PMID: 20713053 [PubMed - as supplied by publisher]
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6.	J Drugs Dermatol. 2010 Jun;9(6):684-6. Pimecrolimus 1% cream in the treatment of cutaneous lesions of pemphigus vulgaris: a double-blind, placebo-controlled clinical trial. Iraji F, Asilian A, Siadat AH. Department of Dermatology, Isfahan University of Medical Sciences Skin Diseases and Leishmaniasis Research Center, Isfahan, Iran. Abstract BACKGROUND: Pemphigus vulgaris (PV) is a chronic, bullous disorder that is usually characterized by the presence of bulla and erosion on the skin and mucosa. Many studies on PV focus on the use of topical non-steroid agents. One of these agents is pimecrolimus; its efficacy is established in some inflammatory and autoimmune disorders such as oral and genital lichen planus. PATIENTS, MATERIALS AND METHODS: This was a double-blind study that was performed in 11 patients with confirmed diagnosis of PV. Patients under treatment with systemic steroid and azathioprine who had bilateral symmetrical oral lesions were selected and right- or left-sided lesions of those identified were randomized to be treated either by pimecrolimus 1% cream or placebo. The largest diameter of lesions was measured at the baseline and every 15 days for two times. Epithelization Index (EI) was calculated and data were analyzed with a program for statistical analysis. RESULTS: Overall, 11 patients (62 cutaneous lesions; 31 lesions in the pimecrolimus group and 31 lesions in the placebo group) with cutaneous lesions of the pemphigus vulgaris were included in this study. At the end of day 15, there was significant difference regarding EI between the pimecrolimus and placebo groups. In addition, EI was significantly different at the end of study (day 30) in favor of pimecrolimus group (P = 0.000). CONCLUSION: Pimecrolimus can be used as an effective and safe adjunctive treatment for cutaneous lesions of pemphigus vulgaris.
	PMID: 20645531 [PubMed - indexed for MEDLINE]
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7.	Eur J Med Chem. 2010 Jul;45(7):2902-11. Epub 2010 Mar 18. Diorganotin(IV) derivatives of ONO tridentate Schiff base: synthesis, crystal structure, in vitro antimicrobial, anti-leishmanial and DNA binding studies. Shujha S, Shah A, Zia-Ur-Rehman, Muhammad N, Ali S, Qureshi R, Khalid N, Meetsma A. Department of Chemistry, Quaid-i-Azam University, Islamabad 45320, Pakistan. Abstract Six new diorganotin(IV) derivatives of N'-(2-hydroxybenzylidene)formohydrazide (H(2)L) with general formula R(2)SnL, where R = Ph (1), Me (2), Bu (3), Oct (4), t-Bu (5), Et (6), and L = [OC(6)H(4)CHNNCHO] have been synthesized and characterized by different analytical techniques. Crystal structure of Me(2)SnL (2) authenticated distorted square-pyramidal geometry around the Sn atom. The CV and UV-Vis spectroscopic data indicated intercalation of complexes into DNA with binding affinity varying in the sequence: 3 (1.69 x 10(4) M(-1)) > 1 (1.10 x 10(4) M(-1)) > 2 (9.61 x 10(3) M(-1)). Some of these compounds were found to be good antibacterial, antifungal and leishmanicidal agents.
	PMID: 20399542 [PubMed - indexed for MEDLINE]
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8.	Eur J Med Chem. 2010 Jul;45(7):2847-53. Epub 2010 Mar 11. Coordination of nitro-thiosemicarbazones to ruthenium(II) as a strategy for a nti-trypanosomal activity improvement. Rodrigues C, Batista AA, Ellena J, Castellano EE, Benítez D, Cerecetto H, González M, Teixeira LR, Beraldo H. Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos (SP), Brazil. Abstract Complexes [RuCl(H4NO(2)Fo4M)(bipy)(dppb)]PF(6) (1), [RuCl(H4NO(2)Fo4M)(Mebipy)(dppb)]PF(6) (2), [RuCl(H4NO(2)Fo4M)(phen)(dppb)]PF(6) (3), [RuCl(H4NO(2)Ac4M)(bipy)(dppb)]PF(6) (4), [RuCl(H4NO(2)Ac4M)(Mebipy)(dppb)]PF(6) (5) and [RuCl(H4NO(2)Ac4M)(phen)(dppb)]PF(6) (6) with N(4)-methyl-4-nitrobenzaldehyde thiosemicarbazone (H4NO(2)Fo4M) and N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M) were obtained from [RuCl(2)(bipy)(dppb)], [RuCl(2)(Mebipy)(dppb)], and [RuCl(2)(phen)(dppb)], (dppb = 1,4-bis(diphenylphospine)butane; bipy = 2,2'-bipyridine; Mebipy = 4,4'-dimethyl-2,2'-bipyridine; phen = 1,10-phenanthroline). In all cases the thiosemicarbazone is attached to the metal center through the sulfur atom. Complexes (1-6), together with the corresponding ligands and the Ru precursors were evaluated for their ability to in vitro suppress the growth of Trypanosoma cruzi. All complexes were more active than their corresponding ligands and precursors. Complexes (1-3) and (5) revealed to be the most active among all studied compounds with ID(50) = 0.6-0.8 microM. In all cases the association of the thiosemicarbazone with ruthenium, dppb and bipyridine or phenanthroline in one same complex proved to be an excellent strategy for activity improvement.
	PMID: 20363536 [PubMed - indexed for MEDLINE]
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