What's new for 'Trypanosomatids' in PubMed

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Sent on Wednesday, 2012 January 04
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 - 5 of 5

4.	Biochemistry. 2011 Nov 22;50(46):10150-8. Epub 2011 Oct 27. Free energy study of the catalytic mechanism of Trypanosoma cruzi trans-sialidase. From the Michaelis complex to the covalent intermediate. Pierdominici-Sottile G, Horenstein NA, Roitberg AE. Source Centro de Estudios e Investigaciones, Universidad Nacional de Quilmes, Sáenz Peña 352, B1876BXD Bernal, Argentina. Abstract Trypanosoma cruzi trans-sialidase (TcTS) is a crucial enzyme for the infection of Trypanosoma cruzi, the protozoa responsible for Chagas' disease in humans. It catalyzes the transfer of sialic acids from the host's glycoconjugates to the parasite's glycoconjugates. Based on kinetic isotope effect (KIE) studies, a strong nucleophilic participation at the transition state could be determined, and recently, elaborate experiments used 2-deoxy-2,3-difluorosialic acid as substrate and were able to trap a long-lived covalent intermediate (CI) during the catalytic mechanism. In this paper, we compute the KIE and address the entire mechanistic pathway of the CI formation step in TcTS using computational tools. Particularly, the free energy results indicate that in the transition state there is a strong nucleophilic participation of Tyr342, and after this, the system collapsed into a stable CI. We find that there is no carbocation intermediate for this reaction. By means of the energy decomposition method, we identify the residues that have the biggest influence on catalysis. This study facilitates the understanding of the catalytic mechanism of TcTS and can serve as a guide for future inhibitor design studies. © 2011 American Chemical Society
	PMID: 22007596 [PubMed - in process]
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5.	Dalton Trans. 2011 Sep 28;40(36):9202-11. Epub 2011 Aug 10. Urease inhibition and anti-leishmanial assay of substituted benzoylguanidines and their copper(II) complexes. Murtaza G, Badshah A, Said M, Khan H, Khan A, Khan S, Siddiq S, Choudhary MI, Boudreau J, Fontaine FG. Source Department of Chemistry, Quaid-i-Azam University, Islamabad, 45320, Pakistan. Abstract A series of N,N',N''-trisubstituted guanidines (1-6) and their copper(II) complexes, [κ(2)(O,N)-C(6)H(5)CONHC(NHC(6)H(4)Cl)NR](2)Cu(ii) (R = iso-propyl (1a), n-butyl (2a), sec-butyl (3a), tert-butyl (4a), benzyl (5a), and para-tolyl (6a)) were synthesized and characterized using elemental analysis, FTIR and NMR spectroscopy. DFT studies were used to assess the location of the protons in the free ligands. However, calculations have shown that, in all cases, hydrogen bonding from either N-H group gives conformations that are very similar in energy. Single crystal XRD studies were used to characterize ligands 1 and 4 and the related complexes 1a and 4a. The structures reveal that these complexes are mononuclear in the solid state and that copper adopts a regular square planar geometry. In both metallic species, the N, N', N''-trisubstituted guanidine ligands chelate the Cu(II) atom using the oxygen and one nitrogen. The synthesized compounds were investigated for urease inhibition using thiourea as a standard drug. Most complexes exhibit a better activity than the respective guanidines and compound 1a was found to be the most active with IC(50) = 9.83 ± 0.07 μM (the IC(50) for thiourea is 21.0 ± 0.1 μM). The species were also screened for their anti-leishmanial activity. However, all of the compounds were devoid of any significant activity. This journal is © The Royal Society of Chemistry 2011
	PMID: 21829831 [PubMed - in process]
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