Naphthylisoquinoline alkaloids and their synthetic analogs as potent novel inhibitors against Babesia canis in vitro.

Babesia canis is the predominant and clinically relevant canine Babesia species in Europe. Transmitted by vector ticks, the parasite enters red blood cells and induces a severe, potentially fatal hemolytic anemia. Here, we report on the antibabesial activities of three extracts of the West African tropical plant species Triphyophyllum peltatum (Dioncophyllaceae) and Ancistrocladus abbreviatus (Ancistrocladaceae) and of 13 genuine naphthylisoquinoline alkaloids isolated thereof. Two of the extracts and eight of the alkaloids were found to display strong activities against Babesia canis in vitro. Among the most potent compounds were the C,C-coupled dioncophyllines A (1a) and C (2) and the N,C-linked alkaloids ancistrocladium A (3) and B (4), with half-maximum inhibition concentration (IC50) values of 0.48 µM for 1a, 0.85 µM for 2, 1.90 µM for 3, and 1.23 µM for 4. Structure-activity relationship (SAR) studies on a small library of related genuine analogs and non-natural synthetic derivatives of 1a and 2 revealed the likewise naturally occurring alkaloid N-methyl-7-epi-dioncophylline A (6b) to be the most potent (IC50, 0.14 µM) among the investigated compounds. Although none of the tested naphthylisoquinolines showed 100 % inhibition of parasite infection - as displayed by imidocarb dipropionate (IC50, 0.07 µM), which was used as a positive control - the antibabesial potential of the dioncophyllines A (1a) and C (2) and related compounds such as 6b, its atropo-diastereomer 6a (IC50, 1.45 µM), and 8-O-(p-nitrobenzyl)dioncophylline A (14) (IC50, 0.82 µM) is to be considered as high. The SAR results showed that N-methylation and axial chirality exert a strong impact on the antibabasial activities of the naphthylisoquinolines presented here, whereas dimerization, as in jozimine A2 (5) (IC50, 140 µM), leads to a significant decrease of activity against B. canis. Alkaloids displaying good to high activities against B. canis like the dioncophyllines 1a, 2, 6a, and 6b were found to cause only a small degree of hemolysis (< 0.7 %), whereas compounds with moderate to weak antibabesial activities such as 6-O-methyl-4'-O-demethylancistrocladine (15a) (IC50, 14.0 µM) and its atropo-diastereomer 6-O-methyl-4'-O-demethylhamatine (15b) (IC50, 830 µM) caused a high degree of hemolysis (7.3 % for 15a and 11.2 % for 15b). In this respect, the most effective anti-Babesia naphthylisoquinolines are also the safest ones.

The associations among the breeding performance of Osmia bicornis L. (Hymenoptera: Megachilidae), burden of pathogens and nest parasites along urbanisation gradient.

Urban environments may negatively affect the development of organisms. In host-pathogen/parasite systems, this impact may lead to increased manifestations of pathogens that decrease the success of their hosts in urban environments compared to rural ones. We tested this hypothesis in the solitary bee Osmia bicornis L. We estimated the development of bees, their reproductive success and the manifestation of different pathogens and nest parasites along an urbanisation gradient. We conducted the experiment in an urbanisation gradient in sites representing three environments: urban, suburban and rural. First, we analysed the manifestation of bacterial and fungal microorganisms in pollen loads, within dried/mummified individuals, on the surface of cocoons and on the surface of diapausing adult individuals by using the MALDI-TOF MS technique. We also verified genetic samples from diapausing individuals for the presence of the parasitic Nosema apis (Zandler, 1909) and N. ceranae (Fries et al., 1996) species. Finally, we assessed the level of reproductive success and manifestations of brood parasites. Not any biological material from the nests was infected by pathogenic microorganisms. This result indicates that the nests are not a reservoir of the pathogenic bacteria and that O. bicornis offspring are not a source or vectors of these pathogens to the surrounding environment and indirectly to other bee species. In urban sites, there was a lower number of parasites than in suburban and rural environments. The presence of parasites was negatively correlated with the reproductive success and may be a limiting factor for O. bicornis populations. We also found that urban sites had the highest indices of reproductive success and the lowest number of breeding failures compared to suburban and rural sites. Moreover, bacterial and fungal transmission is not a serious threat in the studied region.

Topinambur - new possibilities for use in a supplementation diet.

Jerusalem artichoke (Helianthus tuberosus Linne) is a tuberous perennial plant of the Asteraceae family, which originates from North America, and is also known as wild sunflower or topinambur (TPB). It is characterized by good tolerance to frost, drought and poor soil, strong resistance to pests and plant diseases. For ages it was cultivated due to being both an edible tuber and having healing properties. In folk medicine, TPB leaves are used for the treatment of bone fractures and pain. TPB tubers are rich in sugar and have therefore been used for the production of functional food ingredients, such as inulin. Moreover, TPB is one of the potential crops for bioenergy production, such as bioethanol, biobuthanol and biodiesel, and chemicals (lactic acid, butyric acid). A number of bioactive compounds from the above ground parts of this plant have been isolated which have demonstrating antifungal, antioxidant and anticancer activities. In recent years, a number of animal experiments have been carried out to assess the health properties of TPB. Obtained results show that TPB possess a wide spectrum of medical applications, e.g. reduction in the levels of plasma glucose, total cholesterol and triglyceride. Interestingly, TPB has been shown to be a valuable alternative source of prebiotic compounds. This review article presents recent scientific reports on the chemical and biological properties of TPB and its potential use as a prebiotic diet supplement.