Synthesis and anticancer and lipophilic properties of 10-dialkylaminobutynyl derivatives of 1,8- and 2,7-diazaphenothiazines

New derivatives of two isomeric types of azaphenothiazines, 1,8- and 2,7-diazaphenothiazine, containing the triple bond substituents and additionally tertiary cyclic and acyclic amine groups, were synthesized and tested for their anticancer activity. The compounds exhibited differential inhibitory activities. Better results were obtained when the acetylenic group was transformed via the Mannich reaction to the dialkylaminobutynyl groups. The most active was 2,7-diazaphenothiazine with the N-methylpiperazine-2-butynyl substituent against the human ductal breast epithelial tumor cell line T47D, more potent than cisplatin. The 2,7-diazaphenothiazine system turned out to be more active than isomeric 1,8-diaza one. For the most active compound, the expression of TP53, CDKN1A, BCL-2 and BAX genes was detected by the RT-QPCR method. The gene expression ratio BACL-2/BAX suggests the mitochondrial apoptosis in T47D cells. The synthesis makes possible to obtain many new bioactive phenothiazines with the dialkylaminoalkynyl substituents inserting various tertiary cyclic and acyclic amine moieties to the substituents.     

Lipase‐Catalyzed Kinetic Resolution of Novel Antifungal N‐Substituted Benzimidazole Derivatives

A series of new N‐substituted benzimidazole derivatives was synthesized and their antifungal activity against Candida albicans was evaluated. The chemical step included synthesis of appropriate ketones containing benzimidazole ring, reduction of ketones to the racemic alcohols, and acetylation of alcohols to the esters. All benzimidazole derivatives were obtained with satisfactory yields and in relatively short times. All synthesized compounds exhibit significant antifungal activity against Candida albicans 900028 ATCC (% cell inhibition at 0.25 μg concentration > 98%). Additionally, racemic mixtures of alcohols were separated by lipase‐catalyzed kinetic resolution. In the enzymatic step a transesterification reaction was applied and the influence of a lipase type and solvent on the enantioselectivity of the reaction was studied. The most selective enzymes were Novozyme SP 435 and lipase Amano AK from Pseudomonas fluorescens (E > 100). Chirality 28:347–354, 2016. © 2016 Wiley Periodicals, Inc.     

Efficient Detection of Leptosphaeria maculans from Infected Seed lots of Oilseed Rape

An efficient DNA extraction protocol and polymerase chain reaction (PCR) assay for detecting Leptosphaeria maculans from infected seed lots of oilseed rape were developed. L. maculans, the causal agent of blackleg, a damaging disease in oilseeds rape/canola worldwide, was listed as a quarantine disease by China in 2009. China imports several millions of tons of oilseeds every year. So there is a high risk that this pathogen will be introduced to China via contaminated seeds. Seed contamination is one of the most significant factors in the global spread of phytopathogens. Detection of L. maculans in infected seed lots by PCR assay is difficult due to the low level of pathogen mycelium/spores on seeds and PCR inhibitors associated with the seeds of oilseed rape. In our study, these two major obstacles were overcome by the development of a two‐step extraction protocol combined with a nested PCR. This extraction protocol (kit extraction after CTAB method) can efficiently extract high‐quality DNA for PCR. Amplification results showed that the detection threshold for conventional PCR and nested PCR was, respectively, 1 ng and 10 fg of DNA per μl in mycelia samples. On contaminated seed lots of oilseed rape, the detection threshold of conventional and nested PCR was 709 fg/μl and 709 ag/μl of DNA, respectively. The DNA extraction protocol and PCR assay developed in this study can be used for rapid and reliable detection of L. maculans from infected seeds of oilseed rape .     

Isolation and characterization of α‐(1→3)‐glucan‐degrading bacteria from the gut of Diaperis boleti feeding on Laetiporus sulphureus

Bacteria degrading α‐(1→3)‐glucan were sought in the gut of fungivorous insects feeding on fruiting bodies of a polypore fungus Laetiporus sulphureus, which are rich in this polymer. One isolate, from Diaperis boleti, was selected in an enrichment culture in the glucan‐containing medium. The bacterium was identified as Paenibacillus sp. based on the results of the ribosomal DNA analysis. The Paenibacillus showed enzyme activity of 4.97 mU/cm³ and effectively degraded fungal α‐(1→3)‐glucan, releasing nigerooligosaccharides and a trace amount of glucose. This strain is the first reported α‐(1→3)‐glucan‐degrading microorganism in the gut microbiome of insects inhabiting fruiting bodies of polypore fungi.     

Usefulness of multi-parameter opiates-amphetamines-cocainics analysis in hair of drug users for the evaluation of an abuse profile by means of LC-APCI-MS-MS

The report presents a segmental hair analysis for the retrospective multi-parameter evaluation of drugs of abuse including opioids, cocainics and amphetamines. The analysis was carried out with the use of liquid chromatography atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI-MS-MS). The authors have evaluated the differences in the contents of particular opiates in the hair as related to the origin of a sample taken from Polish drug users taking "Polish heroin", and also from heroin abusers from Western European countries taking "Western heroin". The results indicate distinct differences in the 6-MAM concentration values in the Polish and foreigners, suggesting that the foreigners take products containing high concentrations of heroin and the Polish take the poppy product "compote" characterized by its variable and low heroin content. An additional argument for a different abuse profile in the Polish and Western drug users is found in the presence of cocaine detected in hair samples originating from the latter, while cocaine is much less frequently detected in Polish drug users.     

Continuous positive airway pressure treatment in sleep apnea: patient compliance and impact on the right heart

Sleep and Biological Rhythms - Obstructive sleep apnea syndrome (OSAS) is considered to be an important predisposing factor for cardiovascular diseases. The main objective of this study was to...     

Cytogenetic identification of genomic elements of brook trout (Salvelinus fontinalis) in the karyotype of Arctic char (Salvelinus alpinus) from the aquaculture broodstock

Growing interest of Arctic char (Salvelinus alpinus) aquaculture in Europe, and the fact that it can easily hybridize with brook trout (Salvelinus fontinalis) resulting in fertile progeny, led us to investigate fish from the farmed stocks. Chromosomes of sampled Arctic char were examined using conventional and molecular cytogenetic (FISH) techniques in order to determine possible contamination of genomic elements of brook trout. Investigated fish possessed karyotypes composed of 80–82 chromosomes and up to three chromosome fragments. Using staining methods and FISH approach enabled identification of the brook trout chromosomes in the eight out of twenty‐two examined Arctic char. Specific location of AT‐, GC‐ positive and NOR sites observed on chromosomes as well as chromosome fragments in the karyotypes of several individuals points on past chromosomal rearrangements in fish from examined broodstock. Based on our results, it may be assumed that individuals with the brook trout genomic elements, although phenotypically identified as Arctic chars, were hybrids. Our results highlights that special care should be taken to protect gene pools of brook trout and Arctic char in farms where both species are cultured.     

Effects of chronotype and time of day on mood responses to CrossFit training

Morningness-eveningness, time of day, and physical exercises have been shown to influence mood states. This study aimed to test whether impact of physical exercise on mood depends on time of day and chronotype. Ninety-four participants (age 32 ± 6 years; 34% females; weekly training volume 4 ± 1 hours) filled the Composite Scale of Morningness and reported their current mood using the UWIST Mood Adjective Checklist before and after a 60-min long CrossFit training session which took part in the morning (beginning at 6:30 or 7:45) or in the evening (beginning at 19:30 or 20:45). In this quasi-experiment the measurements were taken by the occasion of the participants’ usual training, in their preferred hours. There were only a few evening-types in the studied sample, while morning and intermediate chronotypes were over-represented. Participation in CrossFit training resulted in mood improvement consisting of increase in energetic arousal (η² = 0.29) and hedonic tone (η² = 0.47) and reduction of tense arousal (η² = 0.14), all significant at p = 0.001. Furthermore, CrossFit training during morning hours boosted mood in the intermediate/evening chronotype group to the levels observed in morning chronotypes (η² = 0.29, p < 0.05, for the three-way interaction effect). We conclude that participation in intense physical exercise, such as CrossFit training, may allow compensation for the negative effects of non-optimal time of day on experienced moods, particularly in the case of neither/evening-types.     

Hafnia alvei lipopolysaccharides: Isolation, sugar composition and SDS-PAGE analysis

Abstract Lipopolysaccharides (LPS) of 33 strains of Hafnia alvei were isolated and purified. LPS content of the dry bacterial mass ranged from 1.2 to 4.5%. All examined lipopolysaccharides contained glucose, glucosamine, heptose, 3-deoxy-octulosonic acid and often galactose. Rhamnose, mannose, galactosamine, mannosamine and unidentified amino sugars were found in some H. alvei strains. Sialic acid was present in LPS of one strain. d -3-Hydroxybutyryl groups also were identified in lipopolysaccharides of 5 strains of this genus.
SDS-PAGE of the lipopolysaccharides was presented in the paper. According to these results two core types exist in H. alvei .