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Conventional oral drug formulations for colonic diseases require the administration of high doses of drug to achieve effective drug concentrations at the target site. However, this exposes patients to serious systemic toxicity in order to achieve efficacy. To overcome this problem, an oral drug delivery system was developed by loading a large amount (ca. 34% w/w) of prednisolone into 3-aminopropyl-functionalized mesoporous silica nanoparticles (MCM-NH2) and targeting prednisolone release to the colon by coating the nanoparticle with succinylated ε-polylysine (SPL). We demonstrate for the first time the pH-responsive ability of SPL as a “nanogate” to selectively release prednisolone in the pH conditions of the colon (pH 5.5–7.4) but not in the more acidic conditions of the stomach (pH 1.9) or small intestine (pH 5.0). In addition to targeting drug delivery to the colon, we explored whether the nanoparticles could deliver cargo intracellularly to immune cells (RAW 264.7 macrophages) and intestinal epithelial cells (LS 174T and Caco-2 adenocarcinoma cell lines). To trace uptake, MCM-NH2were loaded with a cell membrane-impermeable dye, sulforhodamine B. The SPL-coated nanoparticles were able to deliver the dye intracellularly to RAW 264.7 macrophages and the intestinal epithelial cancer cells, which offers a highly promising and novel drug delivery system for diseases of the colon such as inflammatory bowel disease and colorectal cancer.

This study reports the isolation and characterization of six new acremine metabolites, 5-chloroacremine A (4), 5-chloroacremine H (5), and acremines O (6), P (7), Q (8), and R (9), together with the known acremines A (1), F (2), and N (3) from the fungus Acremonium persicinumcultured from the marine sponge Anomoianthella rubra. The relative configuration of acremine F (2) was determined by analyses of proton coupling constant values and NOESY data, and the absolute configuration confirmed as (1S, 4S, 6R) by X-ray crystallographic analysis of the borate ester derivative 15. Acremines O, P, and R were each shown to be of 8Rconfiguration by 1H NMR analyses of MPA esters. The relative configurations suggested for acremines P and Q were each deduced by molecular modeling together with NOESY and coupling constant data. The 3JH–Cvalues in acremine P were measured using the pulse sequence EXSIDE, and the observed 3JH8–C4of 5.4 Hz and small 3JH–Cvalues (<1.5 Hz) from H-8 to C-10 and C-11 were fully consistent with stereoisomer 7a. For acremine Q, NOESY data combined with molecular modeling established the preferred diastereomer 8a.

Phytochemical investigation of Chamaelirium luteum(“false unicorn”) resulted in the isolation of 15 steroidal glycosides. Twelve of these (1, 2, 4–9, 11–13, and 15) are apparently unique to this species, and eight of these (6–9, 11–13, and 15) are previously unreported compounds; one (15) possesses a new steroidal aglycone. In addition, the absolute configuration of (23R,24S)-chiograsterol A (10) was defined, and its full spectroscopic characterization is reported for the first time. The structures and configurations of the saponins were determined using a combination of multistage mass spectrometry (MSn), 1D and 2D NMR experiments, and chemical degradation. The antiproliferative activity of nine compounds obtained in the present work, and eight related compounds generated in previous work, was compared in six human tumor cell lines, with aglycones 3and 10and related derivatives 16, 17, 19, and 20all displaying significant antiproliferative activity.

Sixteen new cyclic peroxides (1–16) with a plakortolide skeleton and the methyl ester derivative of a didehydroplakinic acid (17) were isolated from the Australian sponge Plakinastrella clathrataKirkpatrick, 1900. Structural elucidation and configurational assignments were based on spectroscopic analysis and comparison with data for previously isolated plakortolides and revealed both phenyl- and methyl-terminating side chains attached to the plakortolide core. Plakortoperoxides A–D (5–8) each contained a second 1,2-dioxine ring; a cisconfiguration for the side chain endoperoxide ring was determined by a low-temperature NMR study and by comparison of chemical shift values with those of reported compounds. An enantioselective HPLC study compared natural plakortoperoxide A with a synthetic sample prepared by cyclization of plakortolide P with singlet oxygen and revealed that the natural sample was a mixture of cisdiastereomers at C-15/C18. Four other cyclic peroxides (9–12) possessed a C9-truncated side chain terminating in a formyl or carboxylic acid functionality, suggesting that these metabolites may have been formed by oxidative cleavage of the Δ9,10bond of diene-functionalized plakortolides. A final group of four metabolites (13–16) with hydroxy or the rare hydroperoxy functionality unexpectedly revealed a C8side chain, while the ester (17) represents further structural variation within the growing family of cyclic peroxy sponge metabolites.

Investigation of chemical constituents from the bark of Durio carinatushas led to the isolation of three lignans, boehmenan X (1), threo-carolignan X (2), and erythro-carolignan X (3), together with the three known lignans boehmenan, threo-carolignan E, and erythro-carolignan E. The bark of D. oxleyanusyielded two new lignan ethers, threo-carolignan Y (4) and erythro-carolignan Y (5), together with compounds 1, 3, and boehmenan. J-Based configurational analysis and NOE measurements were used to explore conformational issues for the lignan diastereomers, while CD measurements supported an 8′Sconfiguration for the various lignans. The triterpenes 3β-O-cis-caffeoylbetulinic acid and 3β-O-trans-caffeoylbetulinic acid were also characterized from D. carinatus.

A remarkably diverse suite of spiroacetals including a novel member of the rare, branched chain class has been identified in the glandular secretions of Bactrocera tryoni, the most destructive horticultural pest in Australia.