Organometallic gold(iii) complexes with hybrid SNS-donating thiosemicarbazone ligands: cytotoxicity and anti-Trypanosoma cruzi activity.

Stable organogold(iii) compounds of the composition [AuIII(Hdamp)(L1)]Cl are formed from reactions of [AuCl2(damp)] with H2L1 (damp- = dimethylaminomethylphenyl; H2L1 = N'-(diethylcarbamothioyl)benzimidothiosemicarbazides). The cationic complexes can be neutralized by reactions with weak bases under the formation of [AuIII(damp)(L1)] compounds. The structures of the products show interesting features like relatively short AuH contacts between the methylene protons of the Hdamp ligand and the gold(iii) ions. Preliminary biological studies on the uncoordinated compounds H2L1 and their gold complexes indicate considerable cytotoxicity for the [AuIII(Hdamp)(L1)]Cl complexes against MCF-7 cells. The in vitro trypanocidal activity was evaluated against the intracellular form of Trypanosoma cruzi. The organometallic complexes display a remarkable activity, which is dependent on the alkyl substituents of the thiosemicarbazone building blocks of the ligands. One representative of the cationic [AuIII(Hdamp)(L1)]Cl complexes, where H2L1 contains a dimethylthiosemicarbazide building block, shows a trypanocidal activity against the intracellular amastigote form in the same order of magnitude as that of the standard drug benznidazole. Furthermore, no appreciable toxicity to mice spleen cells is observed for this compound resulting in a therapeutic index of about 30, which strongly recommends it as a promising candidate for the development of a future antiparasitic drug.

Enhanced localization, energy anomalous diffusion and resonant mode in harmonic chains with correlated mass-spring disorder.

In this work, we study the vibrational modes and energy spreading in a harmonic chain model with diluted second-neighbors couplings and correlated mass-spring disorder. While all nearest neighbor masses are coupled by an elastic spring, second neighbors springs are introduced with a probability pD. The masses are randomly distributed according to the site connectivity mi = m0 (1 + 1/n(α)(I), where ni is the connectivity of the site i and α is a tunable exponent. We show that maximum localization of the vibrational modes is achieved for α ≃ 3/4. The time-evolution of the energy wave-packet is followed after an initial localized excitation. While the participation number remains finite, the energy spread is shown to be sub-diffusive after a displacement and super-diffusive after an impulse excitation. These features are related to the development of a power-law tail in the wave-packet distribution. Further, we unveil that the spring dilution leads to the emergence of a resonant localized state which is signaled by a van Hove singularity in the density of states.

Resonant localized states and quantum percolation on random chains with power-law-diluted long-range couplings.

We investigate the nature of one-electron eigenstates in power-law-diluted chains for which the probability of occurrence of a bond between sites separated by a distance r decays as p(r) = p/r(1+σ). Using an exact diagonalization scheme and a phenomenological finite-size scaling analysis, we determine the quantum percolation transition phase diagram in the full parameter space (p,σ). We show that the density of states displays singularities at some resonance energies associated with degenerate eigenstates localized in a pair of sites with special symmetries. This model is shown to present an intermediate phase for which there is classical percolation but no quantum percolation. Quantum percolation only takes place for σ < 0.78, a value larger than the corresponding one for the Anderson transition in long-ranged coupled chains with random diagonal disorder. The fractality of critical wavefunctions is also characterized.

Trypanocidal structure-activity relationship for cis- and trans-methylpluviatolide.

The trypanocidal activity of racemic mixtures of cis- and trans-methylpluviatolides was evaluated in vitro against trypomastigote forms of two strains of Trypanosoma cruzi, and in the enzymatic assay of T. cruzi gGAPDH. The cytotoxicity of the compounds was assessed by the MTT method using LLC-MK2 cells. The effect of the compounds on peroxide and NO production were also investigated. The mixture of the trans stereoisomers displayed trypanocidal activity (IC50 approximately 89.3 microM). Therefore, it was separated by chiral HPLC, furnishing the (+) and (-)-enantiomers. Only the (-)-enantiomer was active against the parasite (IC50 approximately 18.7 microM). Despite being inactive, the (+)-enantiomer acted as an antagonistic competitor. Trans-methylpluviatolide displayed low toxicity for LLC-MK2 cells, with an IC50 of 6.53 mM. Furthermore, methylpluviatolide neither inhibited gGAPDH activity nor hindered peroxide and NO production at the evaluated concentrations.

Trypanocidal and antimicrobial activities of Moquinia kingii.

A chloroform crude extract (aerial part) and two compounds, apigenin (1) and cynaropicrin (2), isolated from Moquinia kingii were evaluated against Trypanosoma cruzi trypomastigotes in vitro. Antimicrobial activity was also screened using twenty-two strains including gram-positive and gram-negative bacteria and the yeasts Candida albicans and C. tropicalis. The chloroform crude extract, fractions and isolated compounds from M. kingii were active for both activities. The IC50 values for trypanocidal activity obtained for cynaropicrin and apigenin were 93.5 microg/ml and 181 microg/ml, respectively, while the minimum inhibitory concentrations (MICs) varied from 100 microg/ml to 2500 microg/ml, against the strains of bacteria and yeasts evaluated.

In vitro activity of Rutaceae species against the trypomastigote form of Trypanosoma cruzi.

The activity of crude plant extracts of nine species of Rutaceae against the trypomastigote form of Trypanosoma cruzi was evaluated at 4 mg/ml. Thirty-two crude extracts were tested and eight of them showed significant activity (>80%). The most active extract was obtained from the stems of Pilocarpus spicatus (97.3%). Fractionation of the active crude extracts provided 25 fractions which were tested against the trypomastigote form of T. cruzi at 2 mg/ml. Of these six showed significant activity (>80%). The most active fractions (100%) were obtained from the leaves of Almeidea coerulea (butanol fraction) and Conchocarpus inopinatus (dichloromethane fraction).

Presence of amastigotes in the Weber's lingual salivary gland of Trypanosoma cruzi-infected mice.

The authors studied histopathologically the presence of amastigotes in the Weber's lingual salivary gland of mice infected with RC strain of Trypanosoma cruzi. Amastigotes were found in Weber's gland acini cells, excretory duct cells, intralobular connective tissue, muscle fibers and inside the acini lumen.

Multiple synostosis syndrome: study of a large Brazilian kindred.

We report a large Brazilian kindred with 28 cases of the autosomal dominant multiple synostosis syndrome. The main anomalies were symphalangism and carpal and tarsal synostoses. Other common findings included synostosis involving other bones, absence of phalanges and nails, short metacarpals, pes planovalgus with prominent lateral border, hypoplastic alae of nose, short upper lip, and dermatoglyphic abnormalities. This may be a variant of the WL syndrome.

Ellis-van Creveld syndrome: report of 15 cases in an inbred kindred.

An inbred kindred with 15 cases of the autosomal recessive Ellis-van Creveld syndrome is reported. The ages of the 12 living affected varied between 3 and 82 years. The main characteristics include polydactyly of the hands and feet and several other skeletal anomalies, oral manifestations, and malformations of the heart in 50% of the living affected.