Description of Ichthyascaris grandis sp. n., redescription of Raphidascaroides halieutaeae Yin, 1983 and new records of some other raphidascaridid and philometrid nematodes from marine fishes off Java, Indonesia.

Examinations of nematodes collected from some marine fishes off the southwestern coast of Java, Indonesia in 2000 and 2001 revealed the presence of the following six species: ascaridoids Ichthyascaris grandis sp. n. from the intestine of Lophiomus setigerus (Vahl), I. cf. longispicula Li, Liu, Liu et Zhang, 2012 from the intestine of Conger cinereus Rüppel, Ichthyascaris sp. from the body cavity of Lobotes surinamensis (Bloch), and Raphidascaroides halieutaeae Yin, 1983 from the intestine of Halieutaea stellata (Vahl), and philometrids Philometra ivaschkini Parukhin, 1976 from the stomach wall of Trichiurus lepturus Linnaeus and P. psettoditis Moravec, Walter et Yuniar, 2012 from the body cavity (liver) of Psettodes erumei (Bloch et Schneider). Descriptions of these nematodes based on light and scanning electron microscopical studies are provided. The new species I. grandis sp. n. is mainly characterised by large body measurements (males and females up to 41.8 mm and 73.6 mm long, respectively), the length of spicules (0.99-1.05 mm), the tail tip usually without rudimentary spines and by the presence of 44-53 pairs of caudal papillae, eight to twelve of which being postanals. In addition to new data on the morphology of R. halieutaeae and other nematodes recorded, the 11 species of Raphidascaroides Yamaguti, 1941 poorly described from marine fishes in South Asia and reviewed in the monograph of Sood (2017) are considered species inquirendae and incertae sedis.

Total synthesis and biological evaluation of seven new anti-inflammatory oxacyclododecindione-type macrolactones.

Through variation of our previously published total synthesis of two highly active anti-inflammatory macrolactones from the oxacyclododecindione family (J. Tauber, M. Rohr, T. Walter, G. Erkel and T. Opatz, Org. Biomol. Chem., 2015, 13, 7813-7821), seven new representatives of this compound class were prepared. Substitution of the 14-hydroxy group in oxacyclododecindione with a methyl substituent provided a readily accessible non-natural analogue which has similar pharmacological properties to the scarcely available natural product. Since the producible amount of substance is therefore no longer restricted by low fermentation yields, extensive in vivo studies become possible for the first time. Based on this finding, further investigations on structure-activity relationships were undertaken by variation of the halogen atom, which showed that exchange or omission of the chloro substituent led to significantly lower binding affinities. Furthermore, it was found that elongation of the crucial and characteristic aliphatic side chain at C-10 also increased the IC50 value in the biological assays of interest.

The fungal metabolite cyclonerodiol inhibits IL-4/IL-13 induced Stat6-signaling through blocking the association of Stat6 with p38, ERK1/2 and p300.

The IL-4/IL-13/Stat6 pathway is the key driver of asthma pathophysiology. Therefore the development of inhibitors that specifically modulate IL-13/IL-4 or the downstream signaling molecules like Stat6 may be useful as a therapeutic strategy for the treatment of asthma and multiple allergic diseases. We have previously identified the fungal 2,6-cyclofarnesane cyclonerodiol as an inhibitor of IL-4 induced Stat6-dependent signaling in the alveolar epithelial cell line A549 using a transcriptional reporter. In this study we investigated the underlying mode of action of cyclonerodiol on the IL-4/IL-13/Stat6 pathway. Cyclonerodiol failed to interfere with activation, nuclear transport or binding of Stat6 to the corresponding consensus sequence on the DNA. Our results showed that cyclonerodiol blocked serine phosphorylation of Stat6 by affecting its association with p38 and Erk1/2. Cyclonerodiol also prevented the recruitment of the transcriptional coactivator p300 and Stat6 acetylation. These findings suggest that cyclonerodiol affects IL-4/IL-13 induced expression of asthma related marker genes by blocking transcriptional activation.

A surprising switch in absolute configuration of anti-inflammatory macrolactones.

Oxacyclododecindione-type macrolactones exhibit highly potent anti-inflammatory activities even at nanomolar concentration. After the determination of the relative configuration of the stereocenters at C14 and C15 by total synthesis of 4-dechloro-14-deoxyoxacyclododecindione and 14-deoxyoxacyclododecindione, the absolute configuration has now been assigned by X-ray crystallography. Surprisingly, the absolute configuration is (14S,15R) which differs for C15 from that of the well-known derivatives of (S)-curvularin. The biological activities of both enantiomers of 14-deoxyoxacyclododecindione, obtained by racemic synthesis and optical resolution, were investigated and the ring conformation of the natural product was compared to that of (S)-curvularin and (R)-dehydrocurvularin.

Total synthesis of two potent anti-inflammatory macrolactones of the oxacyclododecindione type.

An esterification/Friedel-Crafts-cyclization approach permitted the first successful synthetic entry into the oxacyclododecindione subclass of the dihydroxyphenylacetic acid lactone-type natural products. This route allowed the preparation of two highly active anti-inflammatory fungal secondary metabolites 14-deoxyoxacyclododecindione and 14-deoxy-4-dechlorooxacyclododecindione as well as their 14-desmethyl analogues.

Five new species of philometrid nematodes (Philometridae) from marine fishes off Java, Indonesia.

Based on light and scanning electron microscopical studies, the following five species of the Philometridae (Nematoda: Dracunculoidea) are described from female specimens collected from marine fishes off the southwestern coast of Java, Indonesia: Philometra lobotidis sp. n. from the abdominal cavity of the Atlantic tripletail Lobotes surinamensis (Bloch) (Lobotidae, Perciformes); Philometra javaensis sp. n. from the abdominal cavity of the immaculate puffer Arothron immaculatus (Bloch et Schneider) (Tetraodontidae, Tetraodontiformes); Philometra psettoditis sp. n. from the musculature of the Indian spiny turbot Psettodes erumei (Bloch et Schneider) (Psettodidae, Pleuronectiformes); Philometroides indonesiensis sp. n. from the musculature of the hound needlefish Tylosurus crocodilus crocodilus (Péron et Lesueur) (Belonidae, Beloniformes); and Philometroides trichiuri sp. n. from the dorsal fin of the largehead hairtail Trichiurus lepturus Linnaeus (type host) and the savalai hairtail Lepturacanthus savala (Cuvier) (both Trichiuridae, Perciformes). All these new species are distinguished from their congeners parasitizing marine fishes by morphological (mainly the shape and structure of the cephalic and caudal ends and of the oesophagus) and biometrical features. Besides previously known Philometra pellucida (Jägerskiöld, 1893) and Philometra ocularis Moravec, Ogawa, Suzuki, Miyazaki et Donai, 2002, they are the only nominal philometrid species recorded from Indonesian waters.

Crustacean fish parasites from Segara Anakan Lagoon, Java, Indonesia.

The present study is the first investigation on ectoparasites of commercial important fish from Segara Anakan, a brackish water lagoon located at the southern coast of Java, Indonesia. Eight economically important marine fish species (Mugil cephalus, Siganus javus, Scatophagus argus, Caranx sexfasciatus, Lutjanus johnii, Eleutheronema tetradactylum, Johnius coitor, and Epinephelus coioides) were examined for crustacean parasites. Prevalence and intensity data for each parasite species are given, together with an analysis of the origin and possible transmission pathways. A highly divers copepod fauna consisting of 23 different species and two isopods was found. All fish species were at least infested with two copepod species, with the exception of L. johnii, S. argus, and M. cephalus. With seven and six species, respectively, they harboured the most species-rich ectoparasite fauna. The copepods Ergasilus sp. 3 and Caligus acanthopagri on S. argus showed the highest prevalence (78.6) and intensity [17.8 (1-233) and 5.3 (1-22)] of infestation. The recorded parasite fauna is represented by marine, brackish water, and probably also freshwater components. The brackish water environment of Segara Anakan does not prevent disease outbreaks due to parasitic copepods by preventing pathogenic marine or freshwater species to enter the lagoon. This might cause fish health problems if the Segara Anakan Lagoon would be developed for finfish mariculture in future.