Barbara Bartholomew

Synthesis and glycosidase inhibition of the enantiomer of (-)-steviamine, the first example of a new class of indolizidine alkaloid.

(+)-Steviamine, the enantiomer of the natural (-)-steviamine, and its corresponding C5 epimer have been synthesized from the D-ribose-derived cyclic nitrone. (-)-Steviamine was found to be the first naturally occurring iminosugar that causes any inhibition of alpha-galactosaminidases.

Alkaloids from Balanites aegyptiaca

High performance liquid chromatographic (HPLC) analysis of a dichloromethane extract of the stem-barks of Balanites aegyptiaca has yielded two known alkaloids, N-trans-feruloyltyramine (1) and N-cis-feruloyltyramine (2), and three common metabolites, vanillic acid, syringic acid and 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-1-propanone.

Constituents of Cassia laevigata

Calendin (1), cinnamic acid (2), 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (3), 2,3-dihydroxy-1-(4-hydroxy-3-methoxyphenyl)-propan-1-one (4), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-propan-1-one (5), syringic acid (6) and vanillic acid (7) have been isolated from a dichloromethane extract of the leaves and branches of Cassia laevigata.

6-Oxygenated flavones from Baccharis trinervis (Asteraceae)

Sharp, H. J., Bartholomew, B., Bright, C., Latif, Z., Sarker, S. D., Nash, R. J. (2001). 6-oxygenated flavones from Baccharis trinervis (Asteraceae). Biochemical Systematics and Ecology, 29, 105-107. Sponsorship: BBSRC

Sideroxylin and 8-demethylsideroxylin from Eucalyptus saligna (Myrtaceae)

Sarker, S. D., Bartholomew, B., Nash, R. J., Simmonds, M. S. J. (2001). Sideroxylin and 8-demethylsideroxylin from Eucalyptus saligna (Myrtaceae). Biochemical Systematics and Ecology, 29, (7), 759-762. Sponsorship: BBSRC

Totarol, totaradiol and ferruginol: three diterpenes from Thuja plicata (Cupressaceae).

Sharp, H. J., Latif, Z., Bartholomew, B., Bright, C., Jones, C. D., Sarker, S. D., Nash, R. J. (2001). Totarol, totaradiol and ferruginol: three diterpenes from Thuja plicata (Cupressaceae). Biochemical Systematics and Ecology, 29, 215-217. Sponsorship: BBSRC

The Diterpenoid 7-Keto-Sempervirol, Derived from Lycium chinense, Displays Anthelmintic Activity against both Schistosoma mansoni and Fasciola hepatica

Background Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke) and Fasciola hepatica (liver fluke). These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA) (praziquantel for schistosomiasis) or drenching (triclabendazole for fascioliasis) programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. Methodology/ Principle Findings Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB), this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines) and moderately potent (LD50 = 19.1 μM) against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening), oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM). Scanning electron microscopy (SEM) evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental integrity and spine loss. Conclusions/ Significance 7-keto-sempervirol negatively affects the viability and phenotype of two related pathogenic trematodes responsible for significant human and animal infectious diseases. This plant-derived, natural product is also active against both larval and adult developmental forms. As such, the data collectively indicate that 7-keto-sempervirol is an important starting point for anthelmintic drug development. Medicinal chemistry optimisation of more potent 7-keto-sempervirol analogues could lead to the identification of novel chemical entities useful for future combinatorial or replacement anthelmintic control.

Calendin, tyrosol and two benzoic acid derivatives from Veronica persica (Scrophulariaceae)

Veronica persica Poiret (Family: Scrophulariaceae), the `Common Field Speedwella or `Persian speedwella, is a neophytic weed originally from south-west Asia and widely distributed in the temperate regions (USDA-ARS GRIN database, 1999; Fischer, 1987; Holm et al., 1979). The plants were garden weeds and collected in #ower near Aberystwyth (Tyn-y-Graig, Wales), and a voucher specimen (N9623) of this collection has been retained in the herbarium at the Institute of Grassland and Environmental Research (IGER) also known as WPBS, Aberystwyth, Wales.

N-trans-feruloyltyramine from two species of the Solanaceae

Turnock, J., Cowan, S., Watson, A. A., Bartholomew, B., Bright, C., Latif, Z., Sarker, S. D., Nash, R. J. (2001). N-trans-feruloyltyramine from 2 species of the Solanaceae. Biochemical Systematics and Ecology, 29, (2), 209-211. Sponsorship: BBSRC

Emodin and syringaldehyde from Rhamnus pubescens (Rhamnaceae)

Sharp, H. J., Latif, Z., Bartholomew, B., Thomas, D., Thomas, B., Sarker, S. D., Nash, R. J. (2001). Emodin and syringaldehyde from Rhamnus pubescens (Rhamnaceae). Biochemical Systematics and Ecology, 29, (1), 113-115 Sponsorship: BBSRC