Lytic reactions of drugs with lipid membranes (2018)
Journal Article
Britt, H. M., García-Herrero, C. A., Denny, P. W., Mosely, J. A., & Sanderson, J. M. (2019). Lytic reactions of drugs with lipid membranes. Chemical Science, 10(3), 674-680. https://doi.org/10.1039/c8sc04831b

Propranolol is shown to undergo lipidation reactions in three types of lipid membrane: (1) synthetic single-component glycerophospholipid liposomes; (2) liposomes formed from complex lipid mixtures extracted from E. coli or liver cells; and (3) in ce... Read More about Lytic reactions of drugs with lipid membranes.

Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania (2018)
Journal Article
Trinconi, C. T., Miguel, D. C., Silber, A. M., Brown, C., Mina, J. G., Denny, P. W., …Uliana, S. R. (2018). Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania. International Journal for Parasitology: Drugs and Drug Resistance, 8(3), 475-487. https://doi.org/10.1016/j.ijpddr.2018.10.007

Previous work from our group showed that tamoxifen, an oral drug that has been in use for the treatment of breast cancer for over 40 years, is active both in vitro and in vivo against several species of Leishmania, the etiological agent of leishmania... Read More about Tamoxifen inhibits the biosynthesis of inositolphosphorylceramide in Leishmania.

Yeast: bridging the gap between phenotypic and biochemical assays for high-throughput screening (2018)
Journal Article
Denny, P. W. (2018). Yeast: bridging the gap between phenotypic and biochemical assays for high-throughput screening. Expert Opinion on Drug Discovery, 13(12), 1153-1160. https://doi.org/10.1080/17460441.2018.1534826

Introduction: Both in vitro biochemical and phenotypic assay platforms have clear limitations in high throughput screening (HTS) for drug discovery. The use of genetically tractable model yeast as a vehicle for target-based HTS overcomes many of thes... Read More about Yeast: bridging the gap between phenotypic and biochemical assays for high-throughput screening.

Functional analyses of a putative, membrane-bound, peroxisomal import mechanism from the apicomplexan protozoan Toxoplasma gondii (2018)
Journal Article
Mbekeani, A., Stanley, W., Kalel, V., Dohan, N., Zalckvar, E., Scheiner, L., …Denny, P. (2018). Functional analyses of a putative, membrane-bound, peroxisomal import mechanism from the apicomplexan protozoan Toxoplasma gondii. Genes, 9(9), Article 434. https://doi.org/10.3390/genes9090434

Peroxisomes are central to eukaryotic metabolism, including the oxidation of fatty acids—which subsequently provide an important source of metabolic energy—and in the biosynthesis of cholesterol and plasmalogens. However, the presence and nature of p... Read More about Functional analyses of a putative, membrane-bound, peroxisomal import mechanism from the apicomplexan protozoan Toxoplasma gondii.

Identifying inhibitors of the Leishmania inositol phosphorylceramide synthase with antiprotozoal activity using a yeast-based assay and ultra-high throughput screening platform (2018)
Journal Article
Norcliffe, J., Mina, J., Alvarez-Ruiz, E., Cantizani-Perez, J., de Dios-Anton, F., Colmenarejo, G., …Denny, P. (2018). Identifying inhibitors of the Leishmania inositol phosphorylceramide synthase with antiprotozoal activity using a yeast-based assay and ultra-high throughput screening platform. Scientific Reports, 8, Article 3938. https://doi.org/10.1038/s41598-018-22063-9

Leishmaniasis is a Neglected Tropical Disease caused by the insect-vector borne protozoan parasite, Leishmania species. Infection affects millions of the world’s poorest, however vaccines are absent and drug therapy limited. Recently, public-private... Read More about Identifying inhibitors of the Leishmania inositol phosphorylceramide synthase with antiprotozoal activity using a yeast-based assay and ultra-high throughput screening platform.

A complex interplay between sphingolipid and sterol metabolism revealed by perturbations to the Leishmania metabolome caused by miltefosine (2018)
Journal Article
Armitage, E., Alqaisi, A., Godzien, J., Pena, I., Mbekeani, A., Alsonso-Herranz, V., …Barbas, C. (2018). A complex interplay between sphingolipid and sterol metabolism revealed by perturbations to the Leishmania metabolome caused by miltefosine. Antimicrobial Agents and Chemotherapy, 62(5), e02095-17. https://doi.org/10.1128/aac.02095-17

With the World Health Organization reporting over 30,000 deaths and 200-400,000 new cases annually, visceral Leishmaniasis is a serious disease affecting some of the world's poorest people. As drug resistance continues to rise, there is a huge unmet... Read More about A complex interplay between sphingolipid and sterol metabolism revealed by perturbations to the Leishmania metabolome caused by miltefosine.