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Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads (2024)
Journal Article
Agostino, V. S., Buerdsell, M. L., Uliana, S. R. B., Denny, P. W., Coelho, A. C., & Steel, P. G. (2024). Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads. Organic and Biomolecular Chemistry, 22(9), 1812-1820. https://doi.org/10.1039/d3ob02091f

A library of hybrid molecules is developed based on the common chemical features shared by clemastine and tamoxifen both of which are well known for their antileishmanial activities. In the initial screening against Leishmania major and L. amazonensi... Read More about Clemastine/tamoxifen hybrids as easily accessible antileishmanial drug leads.

Repurposing as a Strategy for the Discovery of New Anti-Leishmanials: The-State-of-the-Art (2017)
Journal Article
Charlton, R., Rossi-Bergmann, B., Denny, P. W., & Steel, P. G. (2018). Repurposing as a Strategy for the Discovery of New Anti-Leishmanials: The-State-of-the-Art. Parasitology, 145(2), 219-236. https://doi.org/10.1017/s0031182017000993

Leishmaniasis is a vector-borne neglected tropical disease caused by protozoan parasites of the genus Leishmania for which there is a paucity of effective viable non-toxic drugs. There are 1·3 million new cases each year causing considerable socio-ec... Read More about Repurposing as a Strategy for the Discovery of New Anti-Leishmanials: The-State-of-the-Art.

Enlarging the chemical space of anti-leishmanials: a structure-activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis (2016)
Journal Article
Bolt, H., Eggimann, G., Denny, P., & Cobb, S. (2016). Enlarging the chemical space of anti-leishmanials: a structure-activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis. MedChemComm, 7(5), 799-805. https://doi.org/10.1039/c6md00060f

Peptoids, a class of peptide mimetics, have emerged as promising anti-infective agents against a range of bacterial and fungal infections. Recently we have shown peptoids to be novel anti-parasitic and, specifically, anti-leishmanial, compounds. In t... Read More about Enlarging the chemical space of anti-leishmanials: a structure-activity relationship study of peptoids against Leishmania mexicana, a causative agent of cutaneous leishmaniasis.

Crystal Structure of a Hidden Protein, YcaC, a Putative Cysteine Hydrolase from Pseudomonas aeruginosa, with and without an Acrylamide Adduct (2015)
Journal Article
Grøftehauge, M., Truan, D., Vasil, A., Denny, P., Vasil, M., & Pohl, E. (2015). Crystal Structure of a Hidden Protein, YcaC, a Putative Cysteine Hydrolase from Pseudomonas aeruginosa, with and without an Acrylamide Adduct. International Journal of Molecular Sciences, 16(7), 15971-15984. https://doi.org/10.3390/ijms160715971

As part of the ongoing effort to functionally and structurally characterize virulence factors in the opportunistic pathogen Pseudomonas aeruginosa, we determined the crystal structure of YcaC co-purified with the target protein at resolutions of 2.34... Read More about Crystal Structure of a Hidden Protein, YcaC, a Putative Cysteine Hydrolase from Pseudomonas aeruginosa, with and without an Acrylamide Adduct.

The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides (2015)
Journal Article
Eggimann, G., Sweeney, K., Bolt, H., Rozatian, N., Cobb, S., & Denny, P. (2015). The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides. Molecules, 20(2), 2775-2785. https://doi.org/10.3390/molecules20022775

Natural product antimicrobial peptides (AMPs) have been proposed as promising agents against the Leishmania species, insect vector borne protozoan parasites causing the neglected tropical disease leishmaniasis. However, recent studies have shown that... Read More about The Role of Phosphoglycans in the Susceptibility of Leishmania mexicana to the Temporin Family of Anti-Microbial Peptides.

Investigating the Anti-leishmanial Effects of Linear Peptoids (2014)
Journal Article
Eggimann, G., Bolt, H., Denny, P., & Cobb, S. (2015). Investigating the Anti-leishmanial Effects of Linear Peptoids. ChemMedChem, 10(3), 233-237. https://doi.org/10.1002/cmdc.201402416

Peptoids, a class of peptide mimetics, have emerged as promising anti-infective agents against a range of bacterial infections. Herein we present the first study of the antiparasitic and specifically the anti-leishmanial properties of linear peptoids... Read More about Investigating the Anti-leishmanial Effects of Linear Peptoids.

Yeast as a Potential Vehicle for Neglected Tropical Disease Drug Discovery (2014)
Journal Article
Denny, P., & Steel, P. (2015). Yeast as a Potential Vehicle for Neglected Tropical Disease Drug Discovery. Journal of biomolecular screening, 20(1), 56-63. https://doi.org/10.1177/1087057114546552

High-throughput screening (HTS) efforts for neglected tropical disease (NTD) drug discovery have recently received increased attention because several initiatives have begun to attempt to reduce the deficit in new and clinically acceptable therapies... Read More about Yeast as a Potential Vehicle for Neglected Tropical Disease Drug Discovery.

The utility of yeast as a tool for cell-based, target-directed high-throughput screening (2014)
Journal Article
Norcliffe, J., Alvarez-Ruiz, E., Martin-Plaza, J., Steel, P., & Denny, P. (2014). The utility of yeast as a tool for cell-based, target-directed high-throughput screening. Parasitology, 141(1), 8-16. https://doi.org/10.1017/s0031182013000425

Many Neglected Tropical Diseases (NTDs) have recently been subject of increased focus, particularly with relation to high-throughput screening (HTS) initiatives. These vital endeavours largely rely of two approaches, in vitro target-directed screenin... Read More about The utility of yeast as a tool for cell-based, target-directed high-throughput screening.

Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing (2013)
Journal Article
Trmčić, M., Chadbourne, F., Brear, P., Denny, P., Cobb, S., & Hodgson, D. (2013). Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing. Organic and Biomolecular Chemistry, 11(16), 2660-2675. https://doi.org/10.1039/c3ob27448a

We recently reported the use of PSCl3 for the thiophosphorylation of alkylamines where the resulting N-thiophosphoramidate ions could be readily S-alkylated (Chem. Commun., 2011, 47, 6156–6158.). Herein we report the development of this methodology u... Read More about Aqueous synthesis of N,S,-dialkylthiophosphoramidates: design, optimisation and application to library construction and antileishmanial testing.

Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii (2013)
Journal Article
Pratt, S., Wansadhipathi-Kannangara, N., Bruce, C., Mina, J., Shams-Eldin, H., Casas, J., …Denny, P. (2013). Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii. Molecular and Biochemical Parasitology, 87(1), 43-51. https://doi.org/10.1016/j.molbiopara.2012.11.007

Sphingolipids are essential components of eukaryotic cell membranes, particularly the plasma membrane, and are involved in a diverse array of signal transduction pathways. Mammals produce sphingomyelin (SM) as the primary complex sphingolipid via the... Read More about Sphingolipid synthesis and scavenging in the intracellular apicomplexan parasite, Toxoplasma gondii.

Lipid Metabolism as a Therapeutic Target (Editorial) (2012)
Journal Article
Smith, T., Reynolds, T., & Denny, P. (2012). Lipid Metabolism as a Therapeutic Target (Editorial). Biochemistry Research International, 2012, Article 158139. https://doi.org/10.1155/2012/158139

Targeting lipid metabolism (biosynthesis and catabolism) associated with human diseases and pathogens with therapeutics has gained much momentum in recent years. This has come about in part due to the wide availability of sequenced genomes, the advan... Read More about Lipid Metabolism as a Therapeutic Target (Editorial).

Sphingolipid and ceramide homeostasis, potential therapeutic targets (2012)
Journal Article
Young, S., Mina, J., Denny, P., & Smith, T. (2012). Sphingolipid and ceramide homeostasis, potential therapeutic targets. Biochemistry Research International, 2012, Article 248135. https://doi.org/10.1155/2012/248135

Sphingolipids are ubiquitous in eukaryotic cells where they have been attributed a plethora of functions from the formation of structural domains to polarized cellular trafficking and signal transduction. Recent research has identified and characteri... Read More about Sphingolipid and ceramide homeostasis, potential therapeutic targets.

Endocytosis and sphingolipid scavenging in Leishmania mexicana amastigotes (2011)
Journal Article
Ali, H., Harding, C., & Denny, P. (2012). Endocytosis and sphingolipid scavenging in Leishmania mexicana amastigotes. Biochemistry Research International, 2012, Article 691363. https://doi.org/10.1155/2012/691363

Leishmania species are the causative agents of the leishmaniases, a spectrum of neglected tropical diseases. Amastigote stage parasites exist within macrophages and scavenge host factors for survival, for example, Leishmania species utilise host sphi... Read More about Endocytosis and sphingolipid scavenging in Leishmania mexicana amastigotes.

Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa (2011)
Journal Article
Chadbourne, F., Raleigh, C., Ali, H., Denny, P., & Cobb, S. (2011). Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa. Journal of Peptide Science, 17(11), 751-755. https://doi.org/10.1002/psc.1398

Given the paucity and toxicity of available drugs for leishmaniasis, coupled with the advent of drug resistance, the discovery of new therapies for this neglected tropical disease is recognised as being of the utmost urgency. As such antimicrobial pe... Read More about Studies on the antileishmanial properties of the antimicrobial peptides temporin A, B and 1Sa.

Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain (2011)
Journal Article
Mina, J., Mosely, J., Ali, H., Denny, P., & Steel, P. (2011). Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain. Organic and Biomolecular Chemistry, 9(6), 1823-1830. https://doi.org/10.1039/c0ob00871k

The synthesis of set of ceramide analogues exploring hydrophobicity in the acyl chains and the degree and nature of hydroxylation is described. These have been assayed against the parasitic protozoan enzyme LmjIPCS. These studies showed that whilst t... Read More about Exploring Leishmania major inositol phosphorylceramide synthase (LmjIPCS): insights into the ceramide binding domain.