All Outputs (49)

TREATMENT OF LEISHMANIASIS (2024)
Patent
Denny, P., Steel, P., & Lyne, V. (2024). TREATMENT OF LEISHMANIASIS. WO 2024/084186 A1

The invention relates to compounds of formula (I), which may be used in the treatment of microbial infections. In particular, compounds of formula (I) are effective at treating leishmaniasis. The invention extends to novel compositions, therapies and... Read More about TREATMENT OF LEISHMANIASIS.

Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C–H Functionalization of (Poly)fluoroarenes in Organic Synthesis (2024)
Journal Article
Budiman, Y. P., Perutz, R. N., Steel, P. G., Radius, U., & Marder, T. B. (2024). Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C–H Functionalization of (Poly)fluoroarenes in Organic Synthesis. Chemical Reviews, 124(8), 4822-4862. https://doi.org/10.1021/acs.chemrev.3c00793

The synthesis of organic compounds efficiently via fewer steps but in higher yields is desirable as this reduces energy and reagent use, waste production, and thus environmental impact as well as cost. The reactivity of C–H bonds ortho to fluorine su... Read More about Applications of Transition Metal-Catalyzed ortho-Fluorine-Directed C–H Functionalization of (Poly)fluoroarenes in Organic Synthesis.

Synthesis and vectorial functionalisation of pyrazolo[3,4- c ]pyridines (2023)
Journal Article
Bedwell, E. V., da Silva Emery, F., Clososki, G. C., & Steel, P. G. (2023). Synthesis and vectorial functionalisation of pyrazolo[3,4- c ]pyridines. RSC Advances, 13(49), 34391-34399. https://doi.org/10.1039/d3ra07458g

Heterocycles are a cornerstone of fragment-based drug discovery (FBDD) due to their prevalence in biologically active compounds. However, novel heterocyclic fragments are only valuable if they can be suitably elaborated to compliment a chosen target... Read More about Synthesis and vectorial functionalisation of pyrazolo[3,4- c ]pyridines.

Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages (2023)
Journal Article
Porta, E. O., Gao, L., Denny, P. W., Steel, P. G., & Kalesh, K. (2023). Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages. Microbiology Spectrum, 11(6), Article e02960-23. https://doi.org/10.1128/spectrum.02960-23

Heat shock protein 90 (HSP90) is an evolutionarily conserved chaperone protein that plays a central role in the folding and maturation of a large array of client proteins. In the unicellular parasite Leishmania, the etiological agent of the neglected... Read More about Inhibition of HSP90 distinctively modulates the global phosphoproteome of Leishmania mexicana developmental stages.

Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach. (2023)
Journal Article
Madu, S. J., Wang, K., Chirumamilla, S. K., Turner, D. B., Steel, P. G., & Li, M. (2023). Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach. Pharmaceutical Research, 40, 2983-3000. https://doi.org/10.1007/s11095-023-03610-0

Miltefosine is the first and only oral medication to be successfully utilized as an antileishmanial agent. However, the drug is associated with differences in exposure patterns and cure rates among different population groups e.g. ethnicity and age (... Read More about Assessing Dose-Exposure-Response Relationships of Miltefosine in Adults and Children using Physiologically-Based Pharmacokinetic Modeling Approach..

Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity (2023)
Journal Article
Dos Santos, N. S. A., Estevez-Castro, C. F., Macedo, J. P., Chame, D. F., Castro-Gomes, T., Santos-Cardoso, M., …Teixeira, S. M. R. (2023). Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity. PLoS Neglected Tropical Diseases, 17(9), Article e0011646. https://doi.org/10.1371/journal.pntd.0011646

Sphingolipids (SLs) are essential components of all eukaryotic cellular membranes. In fungi, plants and many protozoa, the primary SL is inositol-phosphorylceramide (IPC). Trypanosoma cruzi is a protozoan parasite that causes Chagas disease (CD), a c... Read More about Disruption of the inositol phosphorylceramide synthase gene affects Trypanosoma cruzi differentiation and infection capacity.

Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities (2023)
Journal Article
Porta, E. O. J., Kalesh, K., & Steel, P. G. (2023). Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities. Frontiers in Pharmacology, 14(2023), https://doi.org/10.3389/fphar.2023.1233253

Chagas disease is a vector-borne illness caused by the protozoan parasite Trypanosoma cruzi (T. cruzi). It poses a significant public health burden, particularly in the poorest regions of Latin America. Currently, there is no available vaccine, and c... Read More about Navigating drug repurposing for Chagas disease: advances, challenges, and opportunities.

Activity-Based Protein Profiling: A Graphical Review (2023)
Preprint / Working Paper
Porta, E. O. J., & Steel, P. G. Activity-Based Protein Profiling: A Graphical Review

Iridium‐Catalysed C−H Borylation of Fluoroarenes: Insights into the Balance between Steric and Electronic Control of Regioselectivity (2022)
Journal Article
Ding, M., Reuven, J. A., Hones, A. C., Fox, M. A., & Steel, P. G. (2022). Iridium‐Catalysed C−H Borylation of Fluoroarenes: Insights into the Balance between Steric and Electronic Control of Regioselectivity. European Journal of Organic Chemistry, 2022(47), https://doi.org/10.1002/ejoc.202201005

The iridium catalysed C−H borylation of polyfluorinated arenes and heteroarenes occurs rapidly and efficiently. As with other borylation reactions, whilst steric parameters dominate, an underlying electronic influence on reaction selectivity can be o... Read More about Iridium‐Catalysed C−H Borylation of Fluoroarenes: Insights into the Balance between Steric and Electronic Control of Regioselectivity.

Integral Role of Water in the Solid-State Behavior of the Antileishmanial Drug Miltefosine (2022)
Journal Article
Hall, A. V., Gostick, I. E., Yufit, D. S., Marchant, G. Y., Kirubakaran, P., Madu, S. J., Li, M., Steel, P. G., & Steed, J. W. (2022). Integral Role of Water in the Solid-State Behavior of the Antileishmanial Drug Miltefosine. Crystal Growth and Design, 22(10), 6262-6266. https://doi.org/10.1021/acs.cgd.2c00843

Miltefosine is a repurposed anticancer drug and currently the only orally administered drug approved to treat the neglected tropical disease leishmaniasis. Miltefosine is hygroscopic and must be stored at subzero temperatures. In this work, we report... Read More about Integral Role of Water in the Solid-State Behavior of the Antileishmanial Drug Miltefosine.

Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling (2022)
Journal Article
Porta, E. O., Isern, J. A., Kalesh, K., & Steel, P. G. (2022). Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling. Frontiers in Pharmacology, 13, https://doi.org/10.3389/fphar.2022.929493

Leishmaniasis are a group of diseases caused by parasitic protozoa of the genus Leishmania. Current treatments are limited by difficult administration, high cost, poor efficacy, toxicity, and growing resistance. New agents, with new mechanisms of act... Read More about Discovery of Leishmania Druggable Serine Proteases by Activity-Based Protein Profiling.

Plant growth promotion by the interaction of a novel synthetic small molecule with GA‐DELLA function (2022)
Journal Article
Sukiran, N. A., Pollastri, S., Steel, P. G., & Knight, M. R. (2022). Plant growth promotion by the interaction of a novel synthetic small molecule with GA‐DELLA function. Plant Direct, 6(4), Article e398. https://doi.org/10.1002/pld3.398

Synthesized small molecules are useful as tools to investigate hormonal signaling involved in plant growth and development. They are also important as agrochemicals to promote beneficial properties of crops in the field. We describe here the synthesi... Read More about Plant growth promotion by the interaction of a novel synthetic small molecule with GA‐DELLA function.

Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance (2021)
Journal Article
Schwarz, M., Eno, R. F., Freitag-Pohl, S., Coxon, C. R., Straker, H. E., Wortley, D. J., Hughes, D. J., Mitchell, G., Moore, J., Cummins, I., Onkokesung, N., Brazier-Hicks, M., Edwards, R., Pohl, E., & Steel, P. G. (2021). Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance. Organic and Biomolecular Chemistry, 19(42), 9211-9222. https://doi.org/10.1039/d1ob01802g

The evolution and growth of multiple-herbicide resistance (MHR) in grass weeds continues to threaten global cereal production. While various processes can contribute to resistance, earlier work has identified the phi class glutathione-S-transferase (... Read More about Flavonoid-based inhibitors of the Phi-class glutathione transferase from black-grass to combat multiple herbicide resistance.

Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase (2020)
Journal Article
Mina, J. G., Charlton, R. L., Alpizar-Sosa, E., Escrivani, D. O., Brown, C., Alqaisi, A., Borsodi, M. P. G., Figueiredo, C. P., de Lima, E. V., Dickie, E. A., Wei, W., Coutinho-Silva, R., Merritt, A., Smith, T. K., Barrett, M. P., Rossi-Bergmann, B., Denny, P. W., & Steel, P. G. (2021). Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase. ACS Infectious Diseases, 7(1), 47-63. https://doi.org/10.1021/acsinfecdis.0c00546

Current chemotherapeutics for leishmaniasis have multiple deficiencies, and there is a need for new safe, efficacious, and affordable medicines. This study describes a successful drug repurposing approach that identifies the over-the-counter antihist... Read More about Antileishmanial Chemotherapy through Clemastine Fumarate Mediated Inhibition of the Leishmania Inositol Phosphorylceramide Synthase.

Basal stomatal aperture is regulated by GA-DELLAs in Arabidopsis (2020)
Journal Article
Sukiran, N. A., Steel, P. G., & Knight, M. R. (2020). Basal stomatal aperture is regulated by GA-DELLAs in Arabidopsis. Journal of Plant Physiology, 250, Article 153182. https://doi.org/10.1016/j.jplph.2020.153182

Stomatal aperture is tightly regulated in order to achieve the best compromise between gas exchange and water conservation. Steady-state (basal) stomatal aperture is therefore understandably a key component in plant fitness. It has been shown previou... Read More about Basal stomatal aperture is regulated by GA-DELLAs in Arabidopsis.

Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles (2020)
Journal Article
Sousa-Batista, A. J., Arruda-Costa, N., Escrivani, D. O., Reynaud, F., Steel, P. G., & Rossi-Bergmann, B. (2020). Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles. Parasitology, 147(9), 1032-1037. https://doi.org/10.1017/s0031182020000712

Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous inje... Read More about Single-dose treatment for cutaneous leishmaniasis with an easily synthesized chalcone entrapped in polymeric microparticles.

Iridium Catalysed C-H Borylation of Heteroarenes: Balancing steric and electronic regiocontrol (2020)
Journal Article
Wright, J. S., Scott, P. J., & Steel, P. G. (2021). Iridium Catalysed C-H Borylation of Heteroarenes: Balancing steric and electronic regiocontrol. Angewandte Chemie International Edition, 60(6), 2796-2821. https://doi.org/10.1002/anie.202001520

Over the past twenty years, the iridium catalysed borylation of aromatic C‐H bonds has become the method for the synthesis of aromatic organoboron compounds required for many purposes including applications in natural product synthesis, material scie... Read More about Iridium Catalysed C-H Borylation of Heteroarenes: Balancing steric and electronic regiocontrol.

Exploiting C-H Borylation for the Multidirectional Elaboration of 2-Halopyridines (2019)
Journal Article
Reuven, J., Salih, O., Sadler, S., Thomas, C., & Steel, P. (2020). Exploiting C-H Borylation for the Multidirectional Elaboration of 2-Halopyridines. Tetrahedron, 76(3), Article 130836. https://doi.org/10.1016/j.tet.2019.130836

Regioselectively polysubstituted pyridines can be efficiently accessed from 2-halopyridines via a sequence involving C-H borylation, Suzuki-Miyaura cross-coupling and nucleophilic aromatic substitution chemistry.

Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8 (2019)
Journal Article
Escrivani, D. O., Lopes, M. V., Poletto, F., Ferrarini, S. R., Sousa-Batista, A. J., Steel, P. G., Guterres, S. S., Pohlmann, A. R., & Rossi-Bergmann, B. (2020). Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8. Nanomedicine: Nanotechnology, Biology and Medicine, 24, Article 102121. https://doi.org/10.1016/j.nano.2019.102121

Cutaneous leishmaniasis (CL) is a neglected parasitic disease conventionally treated by multiple injections with systemically toxic drugs. Aiming at a more acceptable therapy, we developed lipid-core nanocapsules (LNCs) entrapping the potent antileis... Read More about Encapsulation in lipid-core nanocapsules improves topical treatment with the potent antileishmanial compound CH8.

C-H activation/metalation approaches for the synthesis of indolizine derivatives (2019)
Journal Article
Clososki, G. C., Steel, P. G., Bertallo, C. R. D. S., Arroio, T. R. A. R., Vessecchi, R., Toledo, M. F., & Sadler, S. (2019). C-H activation/metalation approaches for the synthesis of indolizine derivatives. European Journal of Organic Chemistry, 31-32, 5205-5213. https://doi.org/10.1002/ejoc.201900608

The C‐H borylation of indolizines has not previously been reported and in this communication, we describe our preliminary efforts to apply this chemistry to this scaffold and contrast this approach to directed metalation. Through these methodologies... Read More about C-H activation/metalation approaches for the synthesis of indolizine derivatives.