Simple HPLC‐UV for the quantification of a new leishmanicidal candidate (E)‐1‐4(trifluoromethyl) benzylidene)‐5‐(2‐4‐dichlorozoyl) carbonylhydrazine (LASSBio‐1736) in rat plasma for pharmacokinetics assessment

In this study, a sensitive HPLC‐UV assay was developed and validated for the determination of LASSBio‐1736 in rat plasma with sodium diclofenac as internal standard (IS). Liquid–liquid extraction using acetonitrile was employed to extract LASSBio‐1736 and IS from 100 μL of plasma previously basified with NaOH 0.1 M. Chromatographic separation was carried on Waters Spherisorb^®S5 ODS2 C₁₈ column (150 × 4.6 mm, 5 μm) using an isocratic mobile phase composed by water with triethylamine 0.3% (pH 4), methanol and acetonitrile grade (45:15:40, v/v/v) at a flow rate of 1 mL/min. Both LASSBio‐1736 and IS were eluted at 4.2 and 5 min, respectively, with a total run time of 8 min only. The lower limit of quantification was 0.2 μg/mL and linearity between 0.2 and 4 μg/mL was obtained, with an R² > 0.99. The accuracy of the method was >90.5%. The relative standard deviations intra and interday were <6.19 and <7.83%, respectively. The method showed the sensitivity, linearity, precision, accuracy and selectivity required to quantify LASSBio‐1736 in preclinical pharmacokinetic studies according to the criteria established by the US Food and Drug Administration and European Medicines Agency. Copyright © 2016 John Wiley & Sons, Ltd.     

Characterisation of Taxlllaids A–G; Natural Products from Xenorhabdus indica

Six new lipodepsipeptides and an additional linear derivative named taxlllaids A–G ( 1 – 7 ) have been identified in the entomopathogenic bacterium Xenorhabdus indica. The structures of the main compounds have been solved by detailed NMR spectroscopic analysis and the structures of minor derivatives were elucidated by a combination of labelling experiments and detailed MS experiments. The absolute configuration of the taxlllaids was deduced by using the advanced Marfey method and analysis of the biosynthesis gene cluster showing the presence of epimerisation domains, which was subsequently proved to be correct by solid‐phase peptide synthesis of all taxlllaids. The exchange of a single amino acid in the adenylation domain was shown to be responsible for substrate promiscuity of the third A domain, resulting in the incorporation of leucine, phenylalanine or tyrosine. Bioactivity testing revealed the taxlllaids to be weakly active against Plasmodium falciparum and against a number of eukaryotic cell lines.     

Tranexamic Acid Cream Protects Ultraviolet B-induced Photoaging in Balb/c Mice Skin by Increasing Mitochondrial Markers: Changes Lead to Improvement of Histological Appearance

Tranexamic acid (TSA) is widely used as an antiaging treatment for reducing melasma and wrinkles. There are various mechanisms for wrinkle formation, and one of them is due to damage of the mitochondria. Research on mitochondria in the skin is very limited, so we are interested to see the changes that occur after application of TSA cream. We explored the effect of TSA on mitochondrial protein levels (PGC1α, Tom20, COX IV), which had affected to skin histological structure. Thirty male, 6-week-old, Balb/C mice were divided into five groups (negative control, positive control, TSA 3%, TSA 4% and TSA 5%). After 10 days of acclimatization, four groups of mice were exposed to UVB light, of which three groups were given TSA cream for 10 weeks. The skin tissue was excised for protein and histological studies. H&E staining was performed for evaluating histological changes in epidermal thickness and dermal elastosis. TSA treatment on the mice skin increased mitochondrial marker levels and epidermal thickness while decreasing dermal elastosis for all the treatment groups. Topical application of TSA significantly increased mitochondrial biogenesis which may cause alteration in epidermal thickness and reduced dermal elastosis in the histology of mice skin.     

Structure and properties of Na-magadiite dependent on temperature

The mechanism of the thermal behaviour of Na-magadiite at a temperature range from 293–573 K was developed based on X-ray diffraction, DTA, DTL, Q-TG, and gravimetric measurements. A structure model (BRANDT et al.) previously proposed was additionally used. It is possible to show that there probably is a connection between the typical modifications of basal spacing and significant shiftings of silicate sheets. Different steps of dehydration, decrystallization and structure variations can be ascribed to the several thermal transitions. The results depend on sample treatment such as the existent or not existent solid-water vapour interaction and the establishment of equilibrium. It seems that there is a predominance of the first mentioned influence.