RESUMO

We developed poly-ε-caprolactone (PCL)-based nanoparticles containing D-α-tocopherol polyethylene glycol-1000 succinate (TPGS) or Poloxamer 407 as stabilizers to efficiently encapsulate genistein (GN). Two formulations, referred to as PNTPGS and PNPol, were prepared using nanoprecipitation. They were characterized by size and PDI distribution, zeta potential, nanoparticle tracking analysis (NTA), GN association (AE%), infrared spectroscopy (FT-IR), and differential scanning calorimetry (DSC). PNTPGS-GN exhibited a particle size of 141.2 nm, a PDI of 0.189, a zeta potential of -32.9 mV, and an AE% of 77.95%. PNPol-GN had a size of 146.3 nm, a better PDI than PNTPGS-GN (0.150), a less negative zeta potential (-21.0 mV), and an AE% of 68.73%. Thermal and spectrometric analyses indicated that no new compounds were formed, and there was no incompatibility detected in the formulations. Cellular studies revealed that Poloxamer 407 conferred less toxicity to PCL nanoparticles. However, the percentage of uptake decreased compared to the use of TPGS, which exhibited almost 80% cellular uptake. This study contributes to the investigation of stabilizers capable of conferring stability to PCL nanoparticles efficiently encapsulating GN. Thus, the PCL nanoparticle proposed here is an innovative nanomedicine for melanoma therapy and represents a strong candidate for specific pre-clinical and in vivo studie

Assuntos

RESUMO

Neglected tropical diseases remain among the most critical public health concerns in Africa and South America. The drug treatments for these diseases are limited, which invariably leads to fatal cases. Hence, there is an urgent need for new antitrypanosomal drugs. To address this issue, a large number of diverse heterocyclic compounds were prepared. Straightforward synthetic approaches tolerated pre-functionalized structures, giving rise to a structurally diverse set of analogs. We report on a set of 57 heterocyclic compounds with selective activity potential against kinetoplastid parasites. In general, 29 and 19 compounds of the total set could be defined as active against Trypanosoma cruzi and T. brucei brucei, respectively (antitrypanosomal activities <10 µM). The present work discusses the structure-activity relationships of new fused-ring scaffolds based on imidazopyridine/pyrimidine and furopyridine cores. This library of compounds shows significant potential for anti-trypanosomiases drug discovery.

Assuntos

RESUMO

The pampas deer is an endangered species, from which reproductive biology little is known. We aimed to describe and compare the reproductive seasonal patterns of adult and yearling pampas deer stags throughout the year, including morphological traits, testosterone concentration, sperm morphology and cryoresistance pattern changes. Six adult (AS) and five yearling (YS) stags were captured with anesthetic darts once in winter, spring, summer and autumn to study morphological variables, serum testosterone and semen. Adult males were heavier, their neck girth tended to be greater and their testosterone concentration was higher than in YS. Animals were heavier in summer and autumn. Neck girth and testosterone concentration were greater in autumn. Scrotal circumference, testicular volume and gonado-somatic index varied with seasons, decreasing from winter to spring, increasing in summer and remaining in greater values in autumn. Sperm quality had maximum values from summer to winter. However, the cryoresistance ratio of motility score was greater in spring. In conclusion, in the captivity conditions, pampas deer stags seems to present a light seasonal reproductive pattern, with maximum testis size, testosterone secretion and fresh semen quality in autumn. Nevertheless, sperm cryoresistance ratio seemed to remain stable along the year. Although YS were still growing, they achieved similar semen quality than AS.

RESUMO

The pampas deer is an endangered species, from which reproductive biology little is known. We aimed to describe and compare the reproductive seasonal patterns of adult and yearling pampas deer stags throughout the year, including morphological traits, testosterone concentration, sperm morphology and cryoresistance pattern changes. Six adult (AS) and five yearling (YS) stags were captured with anesthetic darts once in winter, spring, summer and autumn to study morphological variables, serum testosterone and semen. Adult males were heavier, their neck girth tended to be greater and their testosterone concentration was higher than in YS. Animals were heavier in summer and autumn. Neck girth and testosterone concentration were greater in autumn. Scrotal circumference, testicular volume and gonado-somatic index varied with seasons, decreasing from winter to spring, increasing in summer and remaining in greater values in autumn. Sperm quality had maximum values from summer to winter. However, the cryoresistance ratio of motility score was greater in spring. In conclusion, in the captivity conditions, pampas deer stags seems to present a light seasonal reproductive pattern, with maximum testis size, testosterone secretion and fresh semen quality in autumn. Nevertheless, sperm cryoresistance ratio seemed to remain stable along the year. Although YS were still growing, they achieved similar semen quality than AS.

Assuntos

RESUMO

The pampas deer is an endangered species, from which reproductive biology little is known. We aimed to describe and compare the reproductive seasonal patterns of adult and yearling pampas deer stags throughout the year, including morphological traits, testosterone concentration, sperm morphology and cryoresistance pattern changes. Six adult (AS) and five yearling (YS) stags were captured with anesthetic darts once in winter, spring, summer and autumn to study morphological variables, serum testosterone and semen. Adult males were heavier, their neck girth tended to be greater and their testosterone concentration was higher than in YS. Animals were heavier in summer and autumn. Neck girth and testosterone concentration were greater in autumn. Scrotal circumference, testicular volume and gonado-somatic index varied with seasons, decreasing from winter to spring, increasing in summer and remaining in greater values in autumn. Sperm quality had maximum values from summer to winter. However, the cryoresistance ratio of motility score was greater in spring. In conclusion, in the captivity conditions, pampas deer stags seems to present a light seasonal reproductive pattern, with maximum testis size, testosterone secretion and fresh semen quality in autumn. Nevertheless, sperm cryoresistance ratio seemed to remain stable along the year. Although YS were still growing, they achieved similar semen quality than AS.(AU)

Assuntos

RESUMO

Ovarian cancer is the most lethal gynecological cancer of female reproductive system. In order to improve the survival rate, some modifications on nanoparticles surfaces have been investigated to promote active targeting of drugs into tumor microenvironment. The aim of this study was the development and characterization of folate-modified (PN-PCX-FA) and unmodified PLGA nanoparticles (PN-PCX) containing paclitaxel for ovarian cancer treatment. Nanocarriers were produced using nanoprecipitation technique and characterized by mean particle diameter (MPD), polydispersity index (PDI), zeta potential (ZP), encapsulation efficiency (EE), DSC, FTIR, in vitro cytotoxicity and cellular uptake. PN-PCX and PN-PCX-FA showed MPD < 150 nm and PDI < 0.2 with high EE (about 90%). Cytotoxicity assays in SKOV-3 cells demonstrated the ability of both formulations to cause cellular damage. PCX encapsulated in PN-PCX-FA at 1 nM showed higher cytotoxicity than PN-PCX. Folate-modified nanoparticles showed a 3.6-fold higher cellular uptake than unmodified nanoparticles. PN-PCX-FA is a promising system to improve safety and efficacy of ovarian cancer treatment. Further in vivo studies are necessary to prove PN-PCX-FA potential.

Assuntos

RESUMO

Lapachol is a natural naphthoquinone with a range of biological effects, including anticancer activity. Microbial transformations of lapachol can lead to the formation of new biologically active compounds. In addition, fungi can produce secondary metabolites that are also important for drug discovery. The goal of this study was to evaluate the ability of filamentous fungi to biotransform lapachol into biologically active compounds and identify secondary metabolites produced in the presence of lapachol. Seven out of nine strains of filamentous fungi tested exhibited the ability to biotransform or biodegrade lapachol. The bioactive derivatives norlapachol and isolapachol were identified among biotransformation products. Moreover, lapachol stimulated the production of pyrrolo-[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methylpropyl) and phenol-2,4-bis-(1,1-dimethylethyl), secondary metabolites already known to have antimicrobial and antioxidant activities. These results open the perspective of using these strains of filamentous fungi for lapachol biotransformation and efficient production of several biologically active compounds.

Assuntos

RESUMO

Schistosomiasis ranks second only to malaria as the most common parasitic disease worldwide. 700 million people are at risk and 240 million are already infected. Praziquantel is the anthelmintic of choice but decreasing efficacy has already been documented. In this work, we exploited the inhibition of Schistosoma mansoni dihydroorotate dehydrogenase (SmDHODH) as a strategy to develop new therapeutics to fight schistosomiasis. A series of quinones (atovaquone derivatives and precursors) was evaluated regarding potency and selectivity against both SmDHODH and human DHODH. The best compound identified is 17 (2-hydroxy-3-isopentylnaphthalene-1,4-dione) with IC50 = 23 ±â€¯4 nM and selectivity index of 30.83. Some of the new compounds are useful pharmacological tools and represent new lead structures for further optimization.

Assuntos

RESUMO

Identification of new antibiotics suitable for the treatment of tuberculosis is required. In addition to selectivity, it is necessary to find new antibiotics that are effective when the tuberculous mycobacteria are resistant to the available therapies. The furo[2,3-b]pyridine core offers potential for this application. Herein, we have described the screening of our in-house library of furopyridines against Mycobacterium tuberculosis and identified a promising selective bioactive compound against different drug-resistant strains of this mycobacteria. The library of compounds was prepared by a CH amination reaction using mild and metal-free conditions, increasing the available information about the reactivity of furo[2,3-b]pyridine core through this reaction.

Assuntos

RESUMO

The objective of this study was to evaluate different chemical stimulants with different flavours such as acids (citric and acetic), sweet (sucrose) and salty (sodium chloride) applied to cotton rolls and compare their effects on the volume, pH and protein concentrations of the saliva collected and the behaviour of dogs during sampling management. As an additional objective, serum cortisol concentrations of saliva samples obtained with or without citric acid and with or without previous pH adjustment were compared. Five clinically healthy were randomly assigned to one of 5 treatments with cottons with different substances: 1) control, 2) citric acid, 3) acetic acid, 4) sodium chloride, 5) sucrose. Each dog received one treatment per day, and in 5 days, all dogs were tested with the five treatments. On each day, cottons were applied to dogs at times 0, 20, 40, 60 and 80 minutes. The cottons with citric acid generated more volume than the rest of the treatments (p<0.0001), and sodium chloride generated more volume than the control and acetic acid (p≤0.03). Cottons with citric acid generated lower pH of saliva than the rest of the treatments (p<0.0001). Cottons with acetic acid generated lower pH than control, sodium chloride and sucrose (p<0.0001). There were no differences in cortisol concentrations between the control samples and those obtained with citric acid, nor between these same samples with and without pH adjusted with buffer. The concentration of proteins in saliva and excitement degree did not change with treatment. Citric acid was more palatable than the rest of the treatments (p<0.0001). Sodium chloride and sucrose were more palatable than control (p<0.05). In conclusion, citric acid was the chemical stimulant that generated greater volume of saliva and greater palatability in dogs. Although the pH of the saliva obtained with citric acid was clearly acidic, its acidic pH did not affect the determination of cortisol by chemiluminescence or RIA. Sodium chloride and sucrose allowed to obtain high volumes of saliva and were more palatable than the control, which can be other interesting options to obtain saliva in case of not being able to use citric acid.