Inhibition of CYP6B1-Mediated Detoxification of Xanthotoxin by Plant Allelochemicals in the Black Swallowtail (Papilio polyxenes)

The structural and biosynthetic diversity of allelochemicals in plants is thought to arise from selection for additive toxicity as a consequence of toxin mixture or for enhanced toxicity as a result of synergism. In order to understand how insects cope with this type of plant defense, we tested the effects of some allelochemicals in host plants of the black swallowtail Papilio polyxenes on the xanthotoxin-metabolic activity of CYP6B1, the principal enzyme responsible for the detoxification of furanocoumarins in this caterpillar. Additionally, the effects of some synthetic compounds not normally encountered by P. polyxenes on CYP6B1 were tested. These studies demonstrate that the integrity of furanocoumarin structure is important for competitive binding to the active site of CYP6B1, even though the carbonyl group on the pyranone ring apparently does not affect its inhibitory capacity, as in the case of furanochromones. Angular furanocoumarins are generally less phototoxic to many organisms than linear furanocoumarins due to their reduced capacity for cross-linking DNA strands, yet they are more toxic than linear furanocoumarins to black swallowtail larvae. This enhanced toxicity in vivo may be due to the ability of angular furanocoumarins to bind to the active site of CYP6B1 without being rapidly metabolized. This binding reduces the availability of CYP6B1 to metabolize other linear furanocoumarins. The structure-activity relationships for methylenedioxyphenyl compounds, flavonoids, imidazole, and imidazole derivatives are also discussed in light of their capacity to inhibit the xanthotoxin-metabolic activity of CYP6B1.     

Richtungsanalyse von Fasern in Betonen auf Basis der Computer‐Tomographie

Für die Festbetoneigenschaften von Faserbetonen sind die Fasermenge, Faserorientierung und Faserverteilung ausschlaggebend. Dies macht eine Überwachung dieser Parameter notwendig, sei es zur Qualitätssicherung auf der Baustelle oder im Bereich der Forschung zur Weiterentwicklung solcher Betone. Gegenüber bisher angewendeten Methoden zur Untersuchung dieser Einflussgrößen eröffnet die Computer‐Tomographie die Möglichkeit, für Betone mit Fasern und Gelegen aller Art die Faserorientierung und Faserverteilung im gesamten Volumen eines Probekörpers zu betrachten und zu analysieren. Direction Analysis of Fibres in Concrete on Basis of Computed Tomography Decisive factors for the improvement of the hardened concrete characteristics of fibre reinforced concrete are the fibre‐volumeratio, fibre‐orientation and fibre‐distribution. The application of fibre reinforced concrete mixtures requires an appropriate control of these characteristics in the context of quality control at the building site as well as in research work done to improve this kind of concretes. Compared to the methods used up to now, the computed tomography offers the possibility to examine and analyze fibre‐orientation and fibre‐distribution in the entire volume of a specimen.     

The Discovery and Structure-Activity Evaluation of (+)-Floyocidin B and Synthetic Analogs

Tuberculosis represents one of the ten most common courses of death worldwide and the emergence of multidrug-resistant M. tuberculosis makes the discovery of novel anti-tuberculosis active structures an urgent priority. Here, we show that (+)-floyocidin B representing the first example of a novel dihydroisoquinoline class of fungus-derived natural products, displays promising antitubercular hit properties. (+)-Floyocidin B was identified by activity-guided extract screening and its structure was unambiguously determined by total synthesis. The absolute configuration was deduced from a key synthesis intermediate by single crystal X-ray diffraction analysis. A hit series was generated by the isolation of further natural congeners and the synthesis of analogs of (+)-floyocidin B. Extensive biological and physicochemical profiling of this series revealed first structure-activity relationships and set the basis for further optimization and development of this novel antitubercular scaffold.