Roger Wilton Moni

Myrtucommulones F−I, Phloroglucinols with Thyrotropin-Releasing Hormone Receptor-2 Binding Affinity from the Seeds of Corymbia scabrida

High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin-releasing hormone (TRH) receptor-2 binding affinity led to the isolation of four new, myrtucommulones F-I (3-6), and two known, myrtucommulones A (1) and D (2), active acylphloroglucinols from the seeds of the Queensland tree Corymbia scabrida. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The relative configuration of the stereogenic centers for all six compounds was deduced from ROESY correlations. This is the first time that myrtucommulone A (1) has been isolated as a single pure compound. The structure of myrtucommulone D (2) has been revised. Myrtucommulones A, D, and F-I showed rat TRH receptor-2 binding affinity with IC50 values of 39, 11, 16, 24, 31, and 16 microM, respectively.

Sideroxylonal C, a new inhibitor of human plasminogen activator inhibitor type-1, from the flowers of Eucalyptus albens

Sideroxylonal C (3), a new phloroglucinol dimer, was isolated from the flowers of Eucalyptus albens through bioassay-guided fractionation. The structure elucidation was based on 1D and 2D NMR experiments, MS analysis, and comparison with sideroxylonals A (1) and B (2). Sideroxylonal C inhibited human plasminogen activator inhibitor type-1 at 4.7 microM without any significant effect on human tissue plasminogen activator.

A Bastadin with Potent and Selective δ-Opioid Receptor Binding Affinity from the Australian Sponge Ianthella flabelliformis

Three new bastadins, bastadin 25 (1), 15-O-sulfonatobastadin 11 (2), and bastadin 26 (3), were isolated from a MeOH extract of the Australian marine sponge Ianthella flabelliformis. Their structures were determined by interpretation of 1D and 2D NMR spectra and mass spectrometry. Bastadin 26 (3) showed potent affinity for the guinea pig delta-opioid receptors with a K(i) value of 100 nM. The other two bastadins had a 100-fold lower affinity. The three compounds were also tested for their affinity to guinea pig micro- and kappa-opioid receptors and shown to have either no affinity or only very weak affinity toward both of these opioid receptors.

Effects of the amphiphilic peptides mastoparan and adenoregulin on receptor binding, G proteins, phosphoinositide breakdown, cyclic AMP generation, and calcium influx

Summary1. The amphiphilic peptide mastoparan is known to affect phosphoinositide breakdown, calcium influx, and exocytosis of hormones and neurotransmitters and to stimulate the GTPase activity of guanine nucleotide-binding regulatory proteins. Another amphiphilic peptide, adenoregulin was recently identified based on stimulation of agonist binding to A1-adenosine receptors.2. A comparison of the effects of mastoparan and adenoregulin reveals that these peptides share many properties. Both stimulate binding of agonists to receptors and binding of GTPγS to G proteins in brain membranes. The enhanced guanyl nucleotide exchange may be responsible for the complete conversion of receptors to a high-affinity state, complexed with guanyl nucleotide-free G proteins.3. Both peptides increase phosphoinositide breakdown in NIH 3T3 fibroblasts. Pertussis toxin partially inhibits the phosphoinositide breakdown elicited by mastoparan but has no effect on the response to adenoregulin.N-Ethylmaleimide inhibits the response to both peptides.4. In permeabilized 3T3 cells, both adenoregulin and mastoparan inhibit GTPγS-stimulated phosphoinositide breakdown. Mastoparan slightly increases basal cyclic AMP levels in cultured cells, followed at higher concentrations by an inhibition, while adenoregulin has minimal effects.5. Both peptides increase calcium influx in cultured cells and release of norepinephrine in pheochromocytoma PC12 cells. The calcium influx elicited by the peptides in 3T3 cells is not markedly altered byN-ethylmaleimide.6. Multiple sites of action appear likely to underlie the effects of mastoparan/adenoregulin on receptors, G proteins, phospholipase C, and calcium.

Using Peer Teaching to Support Co-Operative Learning in Undergraduate Pharmacology.

Abstract We report findings from the second phase of a study of co-operative, group-based assessment in Pharmacology for second-year undergraduates at The University of Queensland, Australia. Students (n = 285) enrolled in the 2006 Bachelor of Science degree program completed a group-based assessment task (weighted 10% of their course). Blended teaching strategies and the task design were modified to support group formation and peer teaching. A Jigsaw teaching strategy was adopted to support a co-operative learning task in which groups created and submitted a Notice of Intent (NOI) or mini grant proposal based on the topic of Drug Dependence. Assessment was 7% from the NOI and 3% from an individual quiz. In post-assessment surveys, students reported more favourable attitudes towards assessment in which group members received the same marks than in a pre-teaching survey. Findings from the post-task assessment survey were that most students worked co-operatively around assessment. Most students reported that peer teaching help them to complete their assignment and their individual quiz (3%) more than working in “expert panels” or group-based writing. Overall marks were high: the mean ± sd for the group-based NOI was 80 ± 13% and for the averaged quiz marks, 73 ± 13%. The need for more detailed study of group dynamics is recommended.

Spongian Diterpenes with Thyrotropin Releasing Hormone Receptor 2 Binding Affinity from Spongia sp.

High-throughput screening of a plant and marine invertebrate extract library to find natural products with rat thyrotropin releasing hormorne (TRH) receptor 2 binding affinity led to the isolation of four new (1-4) and one known (5) spongian diterpene from the sponge Spongia sp. The structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. The absolute configurations of 1-4 were proposed on the basis of analysis of their CD spectra. Diterpenes 1-5 showed rat TRH receptor 2 binding affinity with IC(50) values of 23 microM, 70 microM, 400 microM, 600 microM, and 1 mM, respectively.

Corymbones A and B, Phloroglucinols with Thyrotropin Releasing Hormone Receptor 2 Binding Affinity from the Flowers of Corymbia peltata

High-throughput screeing of a plant and marine invertebrate extract library to find natural products with rat thytotropin releasing hormone receptor 2 binding affinity led to the isolation of two new active acylphloroglucinols, corymbones A and B (1 and 2) from flowers of the Queensland tree Corymbia peltata. Their structures were assigned from interpretation of 2D NMR and high-resolution ESIMS data. Compounds 1 and 2 showed rat TRH receptor 2 binding affinity with IC 50 values of 23 and 19 microM, respectively.

Critical micelle concentration and hemolytic activity--a correlation suggested by the marine sterol, halistanol trisulfate.

The marine natural product, halistanol trisulfate, has a relatively low critical micelle concentration of 0.001% m/v (14.5 microM) and strong hemolytic potency with an EC50 of 0.00046% m/v (6.67 microM). As expected of a detergent, it inhibits the growth of gram-positive but not gram-negative bacteria. The hemolytic activity of halistanol trisulfate and other detergents has been shown to correlate with critical micelle concentration. This correlation may have important implications in the mechanism of membranolytic bioactivity.

The personal response: A novel writing assignment to engage first year students in large human biology classes†

The teaching of highly valued scientific writing skills in the first year of university is challenging. This report describes the design, implementation, and evaluation of a novel written assignment, The Personal Response and accompanying Peer Review, in the course, Human Biology (BIOL1015) at The University of Queensland. These assignments were the first assessment tasks of the course and were set early in the first semester of university. BIOL1015 had a diverse cohort of 319 first year students from five bachelor degree programs, primarily from Pharmacy and Human Movement Studies. Audio files in the form of interviews with eminent biomedical scientists were obtained from a leading public radio program. Students used these files as triggers to submit a short but highly structured assignment written from a personal perspective and in an expressive style. Evaluations revealed that overall, students found the task interesting and challenging. Students performed well, regardless of their background knowledge, disciplinary interest, or preference for topics within human biology. This study demonstrated that The Personal Response was an appropriate task for these first year students of human biology. It represents an alternative to traditional essay writing.

Reversible depigmentation of human melanoma cells by halistanol trisulphate, a novel marine sterol.

The pigmented human melanoma cell line, MM418, became demelanized when treated continuously with a nontoxic level of halistanol trisulphate (HTS), a C29 steroidal detergent isolated from a marine sponge. Nontoxic levels of halistanol or of a range of anionic, cationic and neutral detergents had no such effect. Control MM418 cells varied greatly in size, appearance and pigmentation; HTS-treated cells were smaller than controls, had a uniform, generally bipolar appearance, and lacked pigment. HTS induced only minor changes in cell ultrastructure, with fewer mature melanosomes being found in treated cells. Suppression of melanin synthesis was apparent within 24 h of addition of HTS, as judged by inhibited incorporation of the false precursor, 5[125I]-2-thiouracil. Reversal of inhibition occurred within the same period after removal of HTS. Tyrosinase activity gradually decreased to 25% of the control value during a 19-day treatment with HTS, and expression of two-carbohydrate-dependent tyrosinase epitopes, 5C12 and 2B7, was abolished. Expression of one other melanosomal protein and of vimentin was not affected. The results suggest that HTS inhibits maturation of tyrosinase to a form associated with melanin synthesis.