Pt(II) and Ag(I) complexes with acesulfame: Crystal structure and a study of their antitumoral, antimicrobial and antiviral activities

Two new complexes of platinum(II) and silver(I) with acesulfame were synthesized. Acesulfame is in the anionic form acesulfamate (ace). The structures of both complexes were determined by X-ray crystallography. For K(2)[PtCl(2)(ace)(2)] the platinum atom is coordinated to two Cl(-) and two N-acesulfamate atoms forming a trans-square planar geometry. Each K(+) ion interacts with two oxygen atoms of the S(=O)(2) group of each acesulfamate. For the polymeric complex [Ag(ace)](n) the water molecule bridges between two crystallographic equivalent Agl atoms which are related each other by a twofold symmetry axis. Two Agl atoms, related to each other by a symmetry centre, make bond contact with two equivalent oxygen atoms. These bonds give rise to infinite chains along the unit cell diagonal in the ac plane. The in vitro cytotoxic analyses for the platinum complex using HeLa (human cervix cancer) cells show its low activity when compared to the vehicle-treated cells. The Ag(I) complex submitted to in vitro antimycobacterial tests, using the Microplate Alamar Blue (MABA) method, showed a good activity against Mycobacterium tuberculosis, responsible for tuberculosis, with a minimal inhibitory concentration (MIC) value of 11.6 mu M. The Ag(I) complex also presented a promising activity against Gram negative (Escherichia colt and Pseudomonas aeruginosa) and Gram positive (Enterococcus faecalis) microorganisms. The complex K(2)[PtCl(2)(ace)(2)] was also evaluated for antiviral properties against dengue virus type 2 (New Guinea C strain) in Vero cells and showed a good inhibition of dengue virus type 2 (New Guinea G strain) replication at 200 mu M, when compared to vehicle-treated cells. (C) 2010 Elsevier Inc. All rights reserved.

Effect of cholesterol on the interaction of the amphibian antimicrobial peptide DD K with liposomes

DD K is an antimicrobial peptide previously isolated from the skin of the amphibian Phyllomedusa distincta. The effect of cholesterol on synthetic DD K binding to egg lecithin liposomes was investigated by intrinsic fluorescence of tryptophan residue, measurements of kinetics of 5(6)-carboxyfluorescein (CF) leakage, dynamic light scattering and isothermal titration microcalorimetry. An 8 nm blue shift of tryptophan maximum emission fluorescence was observed when DD K was in the presence of lecithin liposomes compared to the value observed for liposomes containing 43 mol% cholesterol. The rate and the extent of CF release were also significantly reduced by the presence of cholesterol. Dynamic light scattering showed that lecithin liposome size increase from 115 to 140 nm when titrated with DD K but addition of cholesterol reduces the liposome size increments. Isothermal titration microcalorimetry studies showed that DD K binding both to liposomes containing cholesterol as to liposomes devoid of it is more entropically than enthalpically favored. Nevertheless, the peptide concentration necessary to furnish an adjustable titration curve is much higher for liposomes containing cholesterol at 43 mol% (2 mmol L-1) than in its absence (93 mu mol L-1). Apparent binding constant values were 2160 and 10,000 L mol(-1), respectively. The whole data indicate that DD K binding to phosphatidylcholine liposomes is significantly affected by cholesterol, which contributes to explain the low hemolytic activity of the peptide. (C) 2007 Elsevier Inc. All rights reserved.

Photodynamic therapy for American cutaneous leishmaniasis: The efficacy of methylene blue in hamsters experimentally infected with Leishmania (Leishmania) amazonensis

The aim of this study was to investigate the effectiveness of Photodynamic Therapy (PDT) using Methylene Blue (MB) as the photosensitizing compound and a Light-Emitting Diode (LED) in American cutaneous leishmaniasis (ACL). Hamsters were experimentally infected with Leishmania (Leishmania) amazonensis. After the development of the lesions in the footpad, the animals were treated with MB three times a week for 3 months. Ten minutes after each application of MB, the lesions were irradiated with LED for 1 h. The lesions were evaluated weekly by the measurement of the hamster footpad thickness. At the end of the treatment the parasitic load was quantified in the regional lymph node of the hamsters. The treatment promoted a decrease in the thickness of infected footpad (P = 0.0001) and reduction in the parasitic load in the regional lymph node (P = 0.0007) of the animals from group treated with MB + LED. PDT using MB + LED in ACL caused by L. amazonensis shows a strong photodynamic effect. This therapy is very promising, once it is an inexpensive system and the own patient can apply it in their wound and in their house without the need of technical assistance. (C) 2011 Elsevier Inc. All rights reserved.

Antimicrobial Particles from Cationic Lipid and Polyelectrolytes

Hybrid nanoparticles from cationic lipid and polymers were prepared and characterized regarding physical properties and antimicrobial activity. Carboxymethylcellulose (CMC) and polydiallyldimethylammonium chloride (PDDA) were sequentially added to cationic bilayer fragments (BF) prepared from ultrasonic dispersion in water of the synthetic and cationic lipid dioctadecyldimethylammonium bromide (DODAB). Particles thus obtained were characterized by dynamic light-scattering for determination of z-average diameter (Dz) and zeta-potential (zeta). Antimicrobial activity of the DODAB BF/CMC/PDDA particles against Pseudomonas aeruginosa or Staphylococcus aureus was determined by plating and CFU counting over a range of particle compositions. DODAB BF/CMC/PDDA particles exhibited sizes and zeta-potentials strictly dependent on DODAB, CM C, and PDDA concentrations. At 0.1 mM DODAB, 0.1 mg/mL CMC, and 0.1 mg/mL PDDA, small cationic particles with Dz = 100 nm and zeta = 30 mV were obtained. At 0.5 mM DODAB, 0.5 mg/mL CMC and 0.5 mg/mL PDDA, large cationic particles with Dz = 470 nm and zeta= 50 mV were obtained. Both particulates were highly reproducible regarding physical properties and yielded 0% of p. aeruginosa viability (10(7) CFU/mL) at 1 or 2 mu g/mL PDDA dissolved in solution or in form of particles, respectively. 99% of S. aureus cells died at 10 mu g/mL PDDA alone or in small or large DODAB BF/CMC/PDDA particles. The antimicrobial effect was dependent on the amount of positive charge on particles and independent of particle size. A high microbicide potency for PDDA over a range of nanomolar concentrations was disclosed. P. aeruginosa was more sensitive to all cationic assemblies than S. aureus.

Effects of the antimicrobial peptide gomesin on the global gene expression profile, virulence and biofilm formation of Xylella fastidiosa

In the xylem vessels of susceptible hosts, such as citrus trees, Xylella fastidiosa forms biofilm-like colonies that can block water transport, which appears to correlate to disease symptoms. Besides aiding host colonization, bacterial biofilms play an important role in resistance against antimicrobial agents, for instance antimicrobial peptides (AMPs). Here, we show that gomesin, a potent AMP from a tarantula spider, modulates X. fastidiosa gene expression profile upon 60 min of treatment with a sublethal concentration. DNA microarray hybridizations revealed that among the upregulated coding sequences, some are related to biofilm production. In addition, we show that the biofilm formed by gomesin-treated bacteria is thicker than that formed by nontreated cells or cells exposed to streptomycin. We have also observed that the treatment of X. fastidiosa with a sublethal concentration of gomesin before inoculation in tobacco plants correlates with a reduction in foliar symptoms, an effect possibly due to the trapping of bacterial cells to fewer xylem vessels, given the enhancement in biofilm production. These results warrant further investigation of how X. fastidiosa would respond to the AMPs produced by citrus endophytes and by the insect vector, leading to a better understanding of the mechanism of action of these molecules on bacterial virulence.

Chemical Composition and Antimicrobial Activity of the Essential Oil from Rollinia sericea (REFr.) REFr. (Annonaceae) Leaves

The chemical composition of the essential oil of Rollinia sericea (R.E.Fr.) R.E.Fr. leaves was determined by GC and GC/MS analysis. The analysis revealed the presence mainly of sesquiterpenes: beta-elemene (10%), beta-caryophyllene (10.0%), bicyclogermacrene (9.1%), germacrene-D (8.2%), bicycloelemene (6.2%) and (Z)-nerolidol (5.3%). Rollinia sericea oil was able to inhibit the growth of both fungi Aspergillus niger (16404) and Candida albicans (ATCC 10231) as well as the Gram-positive bacterium Staphyloccocus aureus (ATCC 6538) but it was inactive against the Gram-negative bacteria Escherichia coli (ATCC 8739) and Pseudomonas aeruginosa (ATCC 9027).

Chemical Composition and Antimicrobial Activities of the Essential Oil of Hypericum cordatum (Vell. Conc.) N. Robson (Hypericaceae)

The volatile Constituents of the fresh materials of Hypericum cordatum were isolated by hydrodistillation kind analyzed by CC and GC/MS. The leaves produced 0.04% of a yellowish essential oil and the flowers did not. The main components of the oil were myrcene (40.18%), alpha-pinene (16.40%), and limonene (12%). The antibacterial activities of the oil against Saccharomyces aureus and Escherichia coli and the anti-fungal activities of the oil against the fungi Cladosporium cladosporioides and C. sphaerospemum were evaluated. The oil showed an antibacterial activity against the bacteria S. aureus and anti-fungal activity against the two fungi.

Antimicrobial Activity of Ethylenediaminedisuccinate Metal Complexes

It is shown that metal complexes of the biodegradable ligand ethylenediaminedisuccinic acid (edds) present antimicrobial activity towards fungi and bacteria. [Cd(edds)], in particular, is more toxic than free Cd2+ to Aspergillus niger, behaving as a `Trojan Horse` in the facilitated delivery of the toxic metal into the fungus.

Alkaloids from the Bark of Guatteria hispida and Their Evaluation as Antioxidant and Antimicrobial Agents

Phytochemical investigation of the bark of Guatteria hispida afforded three new alkaloids, 9-methoxy-O-methylmoschatoline (1), 9-methoxyisomoschatoline (2), and isocerasonine (3), along with 10 known alkaloids, 8-oxopseudopalmatine (4), O-methylmoschatoline (5), lysicamine (6), liriodenine (7), 10-methoxyliriodenine (8), nornuciferine (9), anonaine (10), xylopine (11), coreximine (12), and isocoreximine (13). The major compounds, 2, 6, 12, and 13, showed significant antioxidant capacity in the ORAC(FL), assay. Compounds 5, 6, and 7 were active against S. epidermidis and C. dubliniensis, with MIC values in the range 12.5-100 mu g mL(-1).

Chemical Composition and Antimicrobial Activity of the Essential Oil from Croton heterocalyx Baill. (Euphorbiaceae s.s.) Leaves

The chemical composition and the antimicrobial activity of the essential oil from Croton heterocalyx leaves were evaluated. The oil which was analyzed by GC and GUMS was found to contain germacrene D (12.5%), bicyclogermacrene (11.2%), delta-elemene (9.2%) beta-elemene (8.2%), spathulenol (6.9%), linalool (5.4%) and 1,8-cineole (3.7%) its major components. Croton. heterocalyx oil displayed a high inhibitory activity against the fungi Aspergillus niger (16404) and Candida albicans (ATCC 10231.) as well its the Gram-positive bacterium Staphylococcus aureus (ATCC 6538), hut a very weak activity was observed for the Gram-negative bacteria Escherichia coli (ATCC 8739) and Pseudomonas aeruginosa (ATCC 9027).

Complexation of the anti-Trypanosoma cruzi drug benznidazole improves solubility and efficacy

The ruthenium complex,trans-[Ru(Bz)(NH3)(4)SO2](CF3SO3)(2) 1, Bz = benznidazole (N-benzyl-2-(2-nitro-1H-imidazol-1-yl)acetamide), is more hydrosoluble and more active (IC50try/1 h = 79 +/- 3 mu M) than free benznidazole 2 (IC50try/1 h > 1 mM). 1 also exhibits low acute toxicity in vitro (IC50macrophages > 1 mM) and in vivo (400 mu mol/kg < LD50 < 600 mu mol/kg) and the formation of hydroxylamine is more favorable in 1 than in 2 by 9.6 kcal/mol. In murine acute models of Chagas` disease, 1 was more active than 2 even when only one dose was administrated. Moreover, 1 at a thousand-fold smaller concentration than the considered optimal dose for 2 (385 mu mol/kg/day = 100 mg/kg/day), proved to be sufficient to protect all infected mice, eliminating the amastigotes in their hearts and skeletal muscles as observed in H&E micrographics.