New inhibitors of RANKL-induced Osteoclastogenesis from the marine sponge Siphonochalina siphonella.

New sipholane type triterpenes, sipholenols N and O (1 and 2) and neviotine D (3), were isolated from the Red Sea marine sponge Siphonochalina siphonella along with four known triterpenes, sipholenone A (4), sipholenol A (5), siphonellinol D (6) and neviotine A (7). Structure elucidation of 1-3 was achieved by extensive 1D and 2D NMR analyses. The isolated compounds were examined for the inhibition of RANKL induced osteoclastogenesis in RAW264 macrophages. Neviotine D (3) and neviotine A (4) showed potent inhibition with IC50 values of 12.8 and 32.8 µM, respectively.

Diketopiperazines from Costa Rican endolichenic fungus Colpoma sp. CR1465A.

Three new diketopiperazines (1-3), cyclo(l-Pro-d-trans-Hyp) (1), cyclo(l-Pro-d-Glu) (2), and cyclo(d-Pro-d-Glu) (3) and five known diketopiperazines (4-8) were isolated from the endolichenic fungus Colpoma sp. CR1465A identified from the Costa Rican plant Henriettea tuberculosa (Melatomataceae). The structures of the new compounds 1-3 were elucidated using a combination of extensive spectroscopic analyses, including 2D NMR and HR-MS, and their absolute configurations were determined by a combination of NOESY analysis and Marfey's method. Cyclo(l-Pro-d-allo-Thr) (4) was recently isolated from a South China Sea marine sponge Callyspongia sp., but its NMR spectroscopic data were not reported, and cyclo(l-Pro-l-Asp) (5) was previously reported but only as a synthetic product. The NMR data assignments of compounds 4 and 5 are reported for the first time. All of the isolated compounds were tested for antifungal and antimicrobial properties.

Antichlamydial sterol from the Red Sea sponge Callyspongia aff. implexa.

Marine sponges are rich sources of natural products exhibiting diverse biological activities. Bioactivity-guided fractionation of the Red Sea sponge Callyspongia aff. implexa led to the isolation of two new compounds, 26,27-bisnorcholest-5,16-dien-23-yn-3ß,7α-diol, gelliusterol E (1) and C27-polyacetylene, callimplexen A (2), in addition to the known compound ß-sitosterol (3). The structures of the isolated compounds were determined by 1D- and 2D-NMR techniques as well as high-resolution tandem mass spectrometry and by comparison to the literature. The three compounds (1-3) were tested against Chlamydia trachomatis, an obligate intracellular gram-negative bacterium, which is the leading cause of ocular and genital infections worldwide. Only gelliusterol E (1) inhibited the formation and growth of chlamydial inclusions in a dose-dependent manner with an IC50 value of 2.3 µM.

New anti-inflammatory sterols from the Red Sea sponges Scalarispongia aqabaensis and Callyspongia siphonella.

Bioassay-guided fractionation of the anti-inflammation fractions of the Red Sea sponges Scalarispongia aqabaensis and Callyspongia siphonella yielded two new sterols from chloroform fractions of methanol extracts, namely scalaristerol (5alpha,8alpha-dihydroxycholest-6-en-3beta-ol) (1) from Scalarispongia aqabaensis, and callysterol (ergosta-5,11-dien-3beta-ol) (2) from Callyspongia siphonella. Structure determination was based on extensive NMR studies and mass spectrometry. The antiinflammatory activity of compounds 1 and 2 was assessed using the rat-hind paw edema method and by study of their effect on the release of O2(-) and TXB2 from LPS-activated rat neonatal microglia.

Polyacetylene diols with antiproliferative and driving Th1 polarization effects from the marine sponge Callyspongia sp.

A screening of 30 crude extracts of marine sponges against human promyelocytic leukemia cells (HL-60) yielded an EtOAc extract of the sponge Callyspongia sp. (Callyspongiidae) with significant activity. Further bioassay-guided fractionation of the EtOAc extract led to the isolation of three polyacetylene metabolites: a new polyacetylene diol, callyspongidiol (1), along with two known compounds, siphonodiol (2) and 14,15-dihydrosiphonodiol (3). Their structures were determined by a combination of spectroscopic analyses. Compounds 1-3 exhibited antiproliferative activity against HL-60 with IC(50) values of 6.5, 2.8, and 6.5 microg/ml, respectively. These metabolites induce apoptosis in HL-60 cells. Dendritic cells (DC) differentiated with 1-3 enhance the differentiation of naïve T cells towards the Th1 type.