Scalarane-Based Sesterterpenoid RCE-Protease Inhibitors Isolated from the Indonesian Marine Sponge Carteriospongia foliascens

part of research collaboration between Mar Fish Faculty of Unhas and EOS UBCTwo new 20,24-bishomo-25-norscalaranes, compounds 1 and 2, and two new and two known 20,24-bishomoscalaranes, compounds 3???6, have been isolated from the Indonesian marine sponge Carteriospongia foliascens. The structures of 1???6 were determined by spectroscopic analysis. Compounds 1 and 3???6 inhibit RCE-protease activity

Latonduines A and B, New Alkaloids Isolated from the Marine Sponge Stylissa carteri:??? Structure Elucidation, Synthesis, and Biogenetic Implications

Part of research collaboration results between Fac Mar Fish UNHAS and EOS UBCLatonduines A (6) and B (7), two new alkaloids with unprecedented heterocyclic skeletons, have been isolated from the Indonesian marine sponge Stylissa carteri. The structures of the latonduines were elucidated by analysis of spectroscopic data and confirmed by the total synthesis of latonduine A (6). It is proposed that ornithine is the biogenetic precursor to the aminopyrimidine fragment of the latonduines

GARDINERIN, A BIOLOGICALLY ACTIVE ACETOGENIN FROM THE SRI LANKAN GONIOTHALAMUS GARDINERI HOOK. F. AND THOMSON

Objective: The study was undertaken to isolate biologically active compounds from Goniothalamus gardineri, a plant endemic to Sri Lanka. Methods: Roots and flowers of Goniothalamus gardineri were extracted into dichloromethane and methanol. A new acetogenin, gardinerin isolated by column chromatography of the dichloromethane extract was structurally characterized using NMR and Mass spectroscopies. It was found to be mosquito larvicidal (against 2nd instar larvae of Aedes aegypti), cytotoxic (in the brine shrimp assay) and antioxidant (DPPH assay). Results: Gardinerin exhibited potent mosquitolarvicidal activity (LC50 = 0.0744±0.37 ppm.), cytotoxicity (LC50 = 1.5±0.37 ppm) and antioxidant activity (IC50 =10.02±0.01 ppm). The same extract furnished (5R)-goniothalamin. The hexane extract of the flowers of G. gardineri yielded poriferesterol and stigmast-4, 22-dien-3-one.Conclusion: The endemic plant G. gardineri has yielded an acetogenin possessing highly potent antioxidant, cytotoxic and mosquitolarvicidal activity. Â

Resolution and identification of scalemic caged xanthones from the leaf extract of Garcinia propinqua having potent cytotoxicities against colon cancer cells

A new scalemic 8,8a-dihydro caged xanthone (1) was isolated from the leaf extract of Garcinia propinqua. Five other known natural products, the three caged xanthones (2, 5 and 6) and the two neocaged xanthones, (3 and 4) were also isolated as scalemic mixtures. Their structures were characterized by spectroscopic methods. The enantiomeric ratios (er) of compounds 1-6 ranged from 1:0.7 to 1:0.9. These compounds were also resolved by semipreparative chiral HPLC. The absolute configurations of (+)-2 and (+)-3 were determined by single-crystal X-ray diffraction analysis using Cu Kα radiation while the absolute configurations of the other compounds were determined by comparisons of their ECD spectra. Compounds (-)-4, (+)-4, (-)-5, (+)-5, and (-)-6 showed potent cytotoxicities against a colon cancer cell line HCT116 with IC50 values of 2.60, 7.02, 1.47, 3.37, and 4.14μM, respectively, which were better than the standard control doxorubicin (IC50 9.74μM)

Regression of Castrate-Recurrent Prostate Cancer by a Small-Molecule Inhibitor of the Amino-Terminus Domain of the Androgen Receptor

SummaryCastration-recurrent prostate cancer (CRPC) is suspected to depend on androgen receptor (AR). The AF-1 region in the amino-terminal domain (NTD) of AR contains most, if not all, of the transcriptional activity. Here we identify EPI-001, a small molecule that blocked transactivation of the NTD and was specific for inhibition of AR without attenuating transcriptional activities of related steroid receptors. EPI-001 interacted with the AF-1 region, inhibited protein-protein interactions with AR, and reduced AR interaction with androgen-response elements on target genes. Importantly, EPI-001 blocked androgen-induced proliferation and caused cytoreduction of CRPC in xenografts dependent on AR for growth and survival without causing toxicity

Lineage Divergence and Historical Gene Flow in the Chinese Horseshoe Bat (Rhinolophus sinicus)

PMCID: PMC3581519This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

A Multi-Parameter, High-Content, High-Throughput Screening Platform to Identify Natural Compounds that Modulate Insulin and Pdx1 Expression

Diabetes is a devastating disease that is ultimately caused by the malfunction or loss of insulin-producing pancreatic beta-cells. Drugs capable of inducing the development of new beta-cells or improving the function or survival of existing beta-cells could conceivably cure this disease. We report a novel high-throughput screening platform that exploits multi-parameter high-content analysis to determine the effect of compounds on beta-cell survival, as well as the promoter activity of two key beta-cell genes, insulin and pdx1. Dispersed human pancreatic islets and MIN6 beta-cells were infected with a dual reporter lentivirus containing both eGFP driven by the insulin promoter and mRFP driven by the pdx1 promoter. B-score statistical transformation was used to correct systemic row and column biases. Using this approach and 5 replicate screens, we identified 7 extracts that reproducibly changed insulin and/or pdx1 promoter activity from a library of 1319 marine invertebrate extracts. The ability of compounds purified from these extracts to significantly modulate insulin mRNA levels was confirmed with real-time PCR. Insulin secretion was analyzed by RIA. Follow-up studies focused on two lead compounds, one that stimulates insulin gene expression and one that inhibits insulin gene expression. Thus, we demonstrate that multi-parameter, high-content screening can identify novel regulators of beta-cell gene expression, such as bivittoside D. This work represents an important step towards the development of drugs to increase insulin expression in diabetes and during in vitro differentiation of beta-cell replacements