In contrast to FK506 binding proteins and cyclophilins, the parvulin family of peptidyl-prolyl cis/trans isomerases (PPIases; E.C. 5.2.1.8) cannot be inhibited by either FK506 or cyclosporin A. We have found that juglone, 5-hydroxy-1,4-naphthoquinone, irreversibly inhibits the enzymatic activity of several parvulins, like the E. coli parvulin, the yeast Ess1/Ptf1, and human Pin1, in a specific manner, thus allowing selective inactivation of these enzymes in the presence of other PPIases. The mode of action was studied by analyzing the inactivation kinetics and the nature of products of the reaction of E. coli parvulin and its Cys69Ala variant with juglone. For all parvulins investigated, complete inactivation was obtained by a slow process that is characterized by pseudo-first-order rate constants in the range of 5.3 x 10(-)4 to 4. 5 x 10(-)3 s-1. The inactivated parvulin contains two juglone molecules that are covalently bound to the side chains of Cys41 and Cys69 because of a Michael addition of the thiol groups to juglone. Redox reactions did not contribute to the inactivation process. Because thiol group modification was shown to proceed 5-fold faster than the rate of enzyme inactivation, it was considered as a necessary but not sufficient condition for inactivation. When measured by far-UV circular dichroism (CD), the rate of structural alterations following thiol group modification parallels exactly the rate of inactivation. Thus, partial unfolding of the active site of the parvulins was thought to be the cause of the deterioration of PPIase activity.

Summary Comparative analyses of cereal samples pretreated with or without β‐glucosidase indicate the presence of zearalenone‐glycoside. To examine the stability of zearalenone‐glycoside during digestion, mixed feed was artificially contaminated with synthesized zearalenone‐4‐β‐D‐glucopyranoside (395 μg/kg) and fed to a pig over a period of 14 days. The metabolites detected in feces and urine samples were zearalenone and α‐zearalenol. These results demonstrate that zearalenone‐4‐β‐D‐glucopyranoside is decomposed during digestion and the aglucone, zearalenone, is released. Since zearalenone‐glycoside is not detected during routine analysis, but hydrolysed during digestion, it seems likely that such “masked mycotoxins” are involved in cases of mycotoxicoses. Zusammenfassung Vergleichende Analysenergebnisse von Getreideproben, die mit oder ohne β‐Glucosidase vorin‐kubiert wurden, deuten darauf hin, daß glycosylierte Zearalenonkonjugate als natürliche Kontaminan‐ten workommen können. Mischfutter wurde künstlich mit synthetisiertem Zearalenon‐4‐β‐D‐Glucopyranosid versetzt (395 μg/kg) und 14 Tage an ein Schwein verfüttert. In den Harn‐ und Faecesproben wurden ausschließlich Zearalenon und α‐Zearalenol als Metabolite nachgewiesen. Die Resultate dieser Untersuchungen zeigen, daß das Zearalenon‐Glycosid während der Verdauung gespalten und das Aglycon, Zearalenon, freigesetzt wird. Da Zearalenon‐Glycosid bei routinemäßiger Untersuchung nicht detektiert wird, die Verbindung aber nach oraler Aufnahme gespalten wird, ist eine ursächliche Beteiligung derartig „maskierter” Mykotoxine bei der Entstehung klinisch manifester Mykotoxikosen anzunehmen.

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Chemical screening of different Streptomycetes strains resulted in the detection, isolation, and structure elucidation of a number of novel carba-sugars. The constitution of these secondary metabolites, named gabosines A to K (1 to ll), was deduced from spectroscopic data as well as chemical transformation reactions. The gabosines exhibit a basic C7 skeleton and can be characterized as hydroxylated branched cyclohexanone derivatives, which show structural similarities to carbohydrates deriving from secondary metabolism. The configuration fo the gabosines (absolute stereochemistry for 1, 4, 5, and 6; relative configuration for the remaining metabolites) was determined by derivatization with chiral acids (Helmchen's method), NMR spectral analysis, as well as by a comparison of optical rotation values with those of the already known gabosines B (2) and C (3). The new term "ketocarbasugars" is used to characterize a typical ketone containing subgroup of carba-sugars originating from microbial sources. The well available natural gabosines can be used as suitable chiral building blocks.

From Penicillium janczewskii, obtained from a marine sample, two new diastereomeric quinolinones, 3S,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (1) and 3R,4R-dihydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (2), were identified, along with two known alkaloids, peniprequinolone (3) and 3-methoxy-4-hydroxy-4-(4'-methoxyphenyl)-3,4-dihydro-2(1H)-quinolinone (4). Cytotoxicity testing on eight tumor cell lines revealed a moderate specificity of 2 on SKOV-3 cells.

In a continuing search for novel bioactive compounds from marine mangrove plants, seven new naphthoquinone derivatives were isolated from Avicennia marina, namely, avicennone A (1), avicennone B (2), avicennone C (3), avicennone D (4), avicenone E (5), avicennone F (6), and avicennone G (7), along with the known compounds avicequinone A (8), stenocarpoquinone B (9), avicequinone C (10), avicenol A (11), and avicenol C (12). The chemical structures of 1-7 were elucidated by spectroscopic methods. Compounds 8-10, and a mixture of 4 and 5, which all contain a 4,9-dione group, showed strong antiproliferative and moderate cytotoxic activities, as well as antibacterial effects.

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