Cytotoxicity of mini gold nanorods: intersection with extracellular vesicles.

It is well-known that there are size- and shape-dependencies to nanoparticle uptake and processing by living cells. Small gold nanorods have shown to exhibit low toxicity and high clearance rates when compared to larger ones, making smaller particles more desirable for biomedical applications. In this study gold mini-rods (approximately 9.5 × 23, 8 × 26, and 6 × 26 nm, corresponding to aspect ratios 2.5, 3.2 and 4.1) and gold nanospheres (15.6 nm average diameter) were synthesized, and wrapped with cationic and anionic polyelectrolytes. This library of colloidally stable nanomaterials was exposed to human dermal fibroblasts at the relatively low concentration of 1 nM for each nanoparticle type. The cytotoxic profile of these nanoparticles and their influence on the small extracellular vesicles released by the cells was assessed. It was observed that although the nanoparticles were found in vesicles inside the cells, the cell viability, the mitochondrial membrane potential and levels of reactive oxygen species were not markedly affected by the mini gold nanorods. The production of extracellular vesicles by the cells was unaffected by gold nanoparticle exposure; moreover, no gold nanoparticles were observed in extracellular vesicles in the exosomal size range. Taken together, these results suggest that these mini gold nanorods are suitable for a wide range of cellular applications for relatively short-term studies.

Characterization of antimicrobial effect of organotin-based catalysts on diesel-biodiesel deteriogenic microorganisms.

Organotin compounds are applied in several industrial reactions and can present antifungal and antibacterial activities. Incorrect handling and storage practices of biodiesel and diesel-biodiesel blends can lead to microbial development, impacting its final quality. Concerning this problem, this work investigated the antimicrobial action of two organotin catalysts used in biodiesel production with four isolated microroorganisms (Bacillus pumilus, Pseudomonas aeruginosa, Pseudallescheria boydii, and Aureobasidium pullulans) and a pool of microorganisms (ASTM E1259 standard practice). Samples of soybean biodiesel with different concentrations of dibutyl tin dilaurate (catalyst 1) and di-n-butyl-oxo-stannane (catalyst 2) were prepared and added of mineral medium. The pool of microorganisms was inoculated and incubated at 30 °C and final biomass was weighted after 14 days. Thereafter, soybean biodiesel with catalyst 2 was used. Fungal biomass was weighted, and plate count was used to assess bacterial growth. Results show that catalysts 1 and 2 presented no inhibitory activity on the pool of microorganisms evaluated. A slight inhibitory activity was observed for B. pumilus and A. pullulans growth, but not for P. boydii, P. aeruginosa, or the pool of microorganisms. All experiment exhibited acidification higher than sterile control. Infrared analysis show less microbiological degradation products in the tin-protected fuel with ASTM inoculum. These results suggest that these tin-based catalysts show no toxic effect on native microbial population and a slight effect on some isolated microbial population in laboratory scale and for the first time shows that these organotin compounds can be employed safely as biodiesel catalyst. Graphical abstract.

Synthesis and evaluation of the antibiotic and adjuvant antibiotic potential of organotin(IV) derivatives.

A series of organotin(IV) derivatives was investigated in vitro for their antibiotic and adjuvant antibiotic properties (efflux pump inhibitors) against Staphylococcus aureus strains that overexpress efflux pump proteins for norfloxacin (SA-1199B), erythromycin (RN-4220) and tetracycline (IS-58). Most organotin(IV) compounds showed significant antibacterial activity with small Minimum Inhibitory Concentration (MIC) values, some of which were close to 1.0µg/mL (3.1µM), but this feature was also associated with substantial cytotoxicity. Nevertheless, the cytotoxicity of these organotin(IV) compounds can be overcome when they are used as antibiotic adjuvants. Their remarkable adjuvant antibiotic properties allow potentiation of the action of tetracycline (against IS-58 strain) by up to 128-fold. This likely indicates that they can act as putative inhibitors of bacterial efflux pumps. These results reinforce organotin(IV) complexes as promising antibacterial agents, and many of these complexes, if associated with antibiotics, can act as potential adjuvant antibiotic candidates.

Electrochemical Study of Carbon Nanotubes/Nanohybrids for Determination of Metal Species Cu2+ and Pb2+ in Water Samples.

The use of nanomaterials, such as nanoparticles and nanotubes, for electrochemical detection of metal species has been investigated as a way of modifying electrodes by electrochemical stripping analysis. The present study develops a new methodology based on a comparative study of nanoparticles and nanotubes with differential pulse anodic stripping voltammetry (DPASV) and examines the simultaneous determination of copper and lead. The glassy carbon electrode modified by gold nanoparticles demonstrated increased sensitivity and decreased detection limits, among other improvements in analytical performance data. Under optimized conditions (deposition potential -0.8 V versus Ag/AgCl; deposition time, 300 s; resting time, 10 s; pulse amplitude, 50 mV; and voltage step height, 4 mV), the detection limits were 0.2279 and 0.3321 ppb, respectively, for determination of Pb2+ and Cu2+. The effects of cations and anions on the simultaneous determination of metal ions do not exhibit significant interference, thereby demonstrating the selectivity of the electrode for simultaneous determination of Pb2+ and Cu2+. The same method was also used to determine Cu2+ in water samples.

Palladium-benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies.

We synthesized two organometallic diazepam-palladium(II) derivatives by C-H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2 (OAc=acetate). Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl]2 and [(DZP)PdOAc]2, was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP-palladium(II) acetate complex, [(DZP)PdOAc]2, significantly increased (p<0.01 or p<0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl]2, was effective (p<0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP-palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP-palladium(II) complexes as well as evidence that these compounds may play an important role in the study of new drugs to treat patients with epilepsy.

Synthesis and evaluation of the anti-nociceptive and anti-inflammatory activity of 4-aminoquinoline derivatives.

In this paper, we describe the synthesis and pharmacological evaluation of a series of 4-aminoquinolines. The compounds were characterised and tested in models of pain and inflammation, using the writhing test with acetic acid, formalin test, peritonitis test by zymosan and arthritis test with Freund's adjuvant complete assay. The results revealed that all of the 4-aminoquinolines that were prepared promoted anti-nociceptive activity as well as acute and chronic anti-inflammatory effects, with marked activity in the derivates labelled with BAQ and 7-CF3-MAQ. After 7 days of treatment, 7-CF3-MAQ did not induce significant hepatotoxicity, gastrotoxicity or nephrotoxicity.

A very low potential electrochemical detection of L-cysteine based on a glassy carbon electrode modified with multi-walled carbon nanotubes/gold nanorods.

A nanohybrid platform built with multi-walled carbon nanotubes and gold nanorods, prepared via a cationic surfactant-containing seed-mediated sequential growth process, in aqueous solution, on a glassy carbon substrate has been successfully developed to be used in the electrocatalytic oxidation of L-cysteine (Cys). The nanohybrid was characterized by transmission electron microscopy, Raman spectroscopy and electrochemical measurements. Cyclic voltammetry results had shown that the modified electrode allows the oxidation of Cys at a very low anodic potential (0.00 V vs. Ag/AgCl). The kinetic constant kcat for the catalytic oxidation of Cys was evaluated by chronoamperometry and provided a value of 5.6×10(4) L mol(-1) s(-1). The sensor presents a linear response range from 5.0 up to 200.0 µmol L(-1), detection limit of 8.25 nmol L(-1) and a sensitivity of 120 nA L µmol(-1).

Antimalarial activity and mechanisms of action of two novel 4-aminoquinolines against chloroquine-resistant parasites.

Chloroquine (CQ) is a cost effective antimalarial drug with a relatively good safety profile (or therapeutic index). However, CQ is no longer used alone to treat patients with Plasmodium falciparum due to the emergence and spread of CQ-resistant strains, also reported for P. vivax. Despite CQ resistance, novel drug candidates based on the structure of CQ continue to be considered, as in the present work. One CQ analog was synthesized as monoquinoline (MAQ) and compared with a previously synthesized bisquinoline (BAQ), both tested against P. falciparum in vitro and against P. berghei in mice, then evaluated in vitro for their cytotoxicity and ability to inhibit hemozoin formation. Their interactions with residues present in the NADH binding site of P falciparum lactate dehydrogenase were evaluated using docking analysis software. Both compounds were active in the nanomolar range evaluated through the HRPII and hypoxanthine tests. MAQ and BAQ derivatives were not toxic, and both compounds significantly inhibited hemozoin formation, in a dose-dependent manner. MAQ had a higher selectivity index than BAQ and both compounds were weak PfLDH inhibitors, a result previously reported also for CQ. Taken together, the two CQ analogues represent promising molecules which seem to act in a crucial point for the parasite, inhibiting hemozoin formation.