2025
Poon, V. et al. Use of P450 enzymes for late-stage functionalization in drug discovery. J Med Chem https://pubmed.ncbi.nlm.nih.gov/41076635/
Wuyts, E. et al. Biophysical analysis of an oligomerization-attenuated variant of the Leishmania donovani dynamin-1-like protein. Mol Biochem Parasitol 263:111691. https://pubmed.ncbi.nlm.nih.gov/40818547/
Ong, H.B. et al. Comparative metabolism of conjugated and unconjugated pterins in Crithidia, Leishmania and African trypanosomes. PLoS NTD 19: e0013332. https://pubmed.ncbi.nlm.nih.gov/40729363/
Tulloch, L. B. et al (2025) Antitrypanosomal quinazolines targeting lysyl-tRNA synthetase show partial efficacy in a mouse model of acute Chagas disease. Sci Transl Med. 17, adu4564. https://pubmed.ncbi.nlm.nih.gov/40632837/
Wiedemar, N et al. (2025) The thienopyrimidinone gamhépathiopine targets the QO site of Plasmodium falciparum cytochrome b. ACS Infect Dis. 11: 1719-1728. https://pubmed.ncbi.nlm.nih.gov/40460517/
2024
Wall, R.J et al. (2024) ResMAP—a saturation mutagenesis platform enabling parallel profiling of target-specific resistance-conferring mutations in Plasmodium. mBio 0:e01708-24. https://pubmed.ncbi.nlm.nih.gov/39191404/
Tulloch, L.B. et al. (2024) Sterol 14-alpha demethylase (CYP51) activity in Leishmania donovani is likely dependent upon cytochrome P450 reductase 1. PLoS Pathogens 20: e1012382. https://pubmed.ncbi.nlm.nih.gov/38991025/
Khoumeri, O. et al. (2024) Synthesis of Nitrostyrylthiazolidine-2,4-dione Derivatives Displaying Anti-leishmanial Potential. Pharmaceuticals 17, 878. https://doi.org/10.3390/ph17070878
Aguado, M.E. et al. (2024) Identification and Validation of Compounds Targeting Leishmania major Leucyl-Aminopeptidase M17. ACS Infect Dis. 10: 2002-2017. https://pubmed.ncbi.nlm.nih.gov/38753953/
2023
Gonzales, S. et al. (2023) Short-course combination treatment for experimental chronic Chagas disease. Sci Transl Med. 15(726):eadg8105. https://pubmed.ncbi.nlm.nih.gov/38091410/
Brailard, S. et al. (2023) DNDI-6174 is a preclinical candidate for visceral leishmaniasis that targets the cytochrome bc1. Sci Transl Med. 15(726):eadh9902. https://pubmed.ncbi.nlm.nih.gov/38091406/
Tulloch, L. B., Carvalho, S. et al. (2023) RES-Seq—a barcoded library of drug-resistant Leishmania donovani allowing rapid assessment of cross-resistance and relative fitness. mBio. 6:e0180323. https://pubmed.ncbi.nlm.nih.gov/37929970/
Hanna, J. et al. (2023) Mode of action studies confirm on-target engagement of lysyl-tRNA synthetase inhibitor and lead to new selection marker for Cryptosporidium. Front. Cell. Infect. Microbiol. 13:1236814. https://pubmed.ncbi.nlm.nih.gov/37600947/
Wyllie, S. and Fairlamb, A. H. (2023) The critical role of mode of action studies in kinetoplastid drug discovery. Front. Drug. Discov. 3:1185679. https://pubmed.ncbi.nlm.nih.gov/37600222/
Cleghorn, L. et al. (2023) Development of a 2,4-Diaminothiazole series for the treatment of Human African Trypanosomiasis highlights the importance of static-cidal screening of analogues. J. Med. Chem. 66:8896-8916. https://pubmed.ncbi.nlm.nih.gov/37343180/
Bopp, S. et al. (2023) Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation. Nat. Commun. 14:1455. https://pubmed.ncbi.nlm.nih.gov/36927839/
Smith, R. et al. (2023) Chemical pulldown combined with mass spectrometry to identify the molecular targets of antimalarials in cell-free lysates. Star Protocols 4:102002. https://pubmed.ncbi.nlm.nih.gov/36609153/
2022
Navidpour, L. et al. (2022) Antileishmanial Activities of ( Z)-2-(Nitroimidazolylmethylene)-3( 2H)-Benzofuranones: Synthesis, In Vitro Assessment, and Bioactivation by NTR 1 and 2. Antimicrob Agents Chemother. 66: e0058322. https://pubmed.ncbi.nlm.nih.gov/36286539/
Benns, HJ. et al. (2022) CRISPR based oligo recombineering prioritizes apicomplexan cysteines for drug discovery. Nat. Microbiol. 7:1891-1905. https://pubmed.ncbi.nlm.nih.gov/36266336/
Milne, R. et al. (2022) Toolkit of approaches to support target-focused drug discovery for Plasmodium falciparum lysyl tRNA synthetase. ACS Infect. Dis. 8:1962-1974. https://pubmed.ncbi.nlm.nih.gov/36037410/
Tamaki, F. et al. (2022) High-Throughput Screening Platform To Identify Inhibitors of Protein Synthesis with Potential for the Treatment of Malaria. Antimicrob Agents Chemother. (in press). https://pubmed.ncbi.nlm.nih.gov/35647647/
Altmann, S. et al., (2022) Oligo targeting for profiling drug resistance mutations in the parasitic trypanosomatids. Nucleic Acids Res. 50: e79. https://pubmed.ncbi.nlm.nih.gov/35524555/
Smith A, Wall RJ, Patterson S et al., (2022) Repositioning of a diaminothiazole series confirmed to target the cyclin-dependent kinase CRK12 for use in the treatment of African Animal Trypanosomiasis. J Med Chem. 65: 5606-5624. https://pubmed.ncbi.nlm.nih.gov/35303411/
2021
Mowbray, C. Braillard, S., Glossop, P.A., Whitlock, G.A., Jacobs, R.T., Speake, J., Pandi, B., Nare, B., Maes, L.J., Yardley, V., Freund, Y.R., Wall, R.J., Carvalho, S., Bello, D., Van den Kerkhof, M., Caljon, G., Gilbert, I.H., Corpas-Lopez, V., Lukac, I., Patterson, S., Zuccotto, F. and Wyllie, S (2021) DNDI-6148: A novel benzoxaborole preclinical candidate for the treatment of visceral leishmaniasis. J Med Chem. 64:16159-16176. https://pubmed.ncbi.nlm.nih.gov/34711050/
Svensen, N., Wyllie, S., Gray, D.W. and De Rycker, M. (2021) Live-imaging rate-of-kill compound profiling for Chagas disease drug discovery with a new automated high-content assay. PLoS Neglected Tropical Diseases 15(10):e0009870. https://pubmed.ncbi.nlm.nih.gov/34634052/
Lima, M., Tulloch, L.B., Corpas-Lopez, V., Carvalho S., Wall, R.J., Milne, R., Rico, E., Patterson, S., Gilbert, I.H., Moniz, S., MacLean, L., Morgillo, C., Horn, D., Zuccotto, F. and Wyllie, S (2021) Identification of a proteasome-targeting arylsulfonamide with potential for the treatment 1 of Chagas’ disease. Antimicrobial Agents and Chemotherapy. 66(1):e0153521. https://pubmed.ncbi.nlm.nih.gov/34606338/
Barbara Forte et al. (2021) Prioritization of molecular targets for anti-malaria drug discovery. ACS Infect Dis. 7(10):2764-2776. https://pubmed.ncbi.nlm.nih.gov/34523908/
Victoriano Corpas Lopez and Susan Wyllie (2021) Utilizing thermal proteome profiling to identify the molecular targets of anti-leishmanial compounds. Star Protocols. https://star-protocols.cell.com/protocols/948
Juliana da Silva Pacheco et al. (2021) Monocyclic Nitro-heteroaryl Nitrones with Dual Mechanism of Activation: Synthesis and Antileishmanial Activity. ACS Med. Chem. Lett. 12(9):1405-1412. https://pubs.acs.org/doi/10.1021/acsmedchemlett.1c00193
Magali Van den Kerkhof et al. (2021) Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series. Microorganisms. 9:1408. https://pubmed.ncbi.nlm.nih.gov/34210040/
Tuo Yang et al. (2021) MalDA, Accelerating Malaria Drug Discovery. Trends in Parasitology. 37:493-507. https://pubmed.ncbi.nlm.nih.gov/33648890/
Luciana Paradela, Richard J. Wall, Sandra Carvalho, Giulia Chemi, Victoriano Corpas-Lopez, Eoin Moynihan, Davide Bello, Stephen Patterson, Lucia Guther, Alan H. Fairlamb, Michael Ferguson, Fabio Zuccotto, Julio Martin, Ian H. Gilbert and Susan Wyllie. (2021) Multiple unbiased approaches identify oxidosqualene cyclase as the molecular target of a promising anti-leishmanial. Cell Chem. Biol. 28:711-721. https://pubmed.ncbi.nlm.nih.gov/33691122/
Lauren B. Arendse, Susan Wyllie, Kelly Chibale and Ian H. Gilbert. (2021) Plasmodium Kinases as Potential Drug Targets for Malaria: Challenges and Opportunities. ACS Infect Dis. 7:518-534. https://pubmed.ncbi.nlm.nih.gov/33590753/
2020
Cyril Fersing et al. (2020) Antikinetoplastid SAR study in 3-nitroimidazopyridine series: Identification of a novel non-genotoxic and potent anti-T. b. brucei hit-compound with improved pharmacokinetic properties. Eur J Med Chem. 206:112668. https://pubmed.ncbi.nlm.nih.gov/32795774/
Michael G Thomas et al. (2020) Identification and Optimization of a Series of 8-Hydroxy Naphthyridines with Potent In Vitro Antileishmanial Activity: Initial SAR and Assessment of In Vivo Activity. J Med Chem. 63:9523-9539. https://pubmed.ncbi.nlm.nih.gov/32663005/
Cyril Fersing et al. (2020) 8-Alkynyl-3-nitroimidazopyridines display potent antitrypanosomal activity against both T. b. brucei and cruzi. Eur J Med Chem. 202:112558. https://pubmed.ncbi.nlm.nih.gov/32652409/
Julian Pedron et al. (2020) New 8-Nitroquinolinone Derivative Displaying Submicromolar in Vitro Activities against Both Trypanosoma brucei and cruzi. ACS Med Chem Lett.11: 464-472. https://pubmed.ncbi.nlm.nih.gov/32292551/
Richard J. Wall, Sandra Carvalho, Rachel Milne, Juan A. Bueren-Calabuig, Sonia Moniz, Juan Cantizani-Perez,Lorna MacLean, Albane Kessler, Ignacio Cotillo Torrejon, Lalitha Sastry, Sujatha Manthri, Stephen Patterson,Fabio Zuccotto, Stephen Thompson, Julio Martin, Maria Marco, Timothy J. Miles, Manu De Rycker, Michael G. Thomas, Alan H. Fairlamb, Ian H. Gilbert and Susan Wyllie (2020) The Qi site of cytochrome b is a promiscuous drug target in Trypanosoma cruzi and Leishmania donovani. ACS Infect Dis. 6: 515-528. https://pubmed.ncbi.nlm.nih.gov/31967783
2019
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Corpas-Lopez, V., Moniz, S., Thomas, M., Wall, R. J., Torrie, L. S., Zander-Dinse, D. Tinti, M., Brand, S., Stojanovski, L., Manthri, S., Hallyburton, I., Zuccotto, F., Wyatt, P. G., De Rycker, M., Horn, D., Ferguson, M. A. J., Clos, J., Read, K. D., Fairlamb, A.H., Gilbert, I. H. and Wyllie, S. (2019) Pharmacological validation of N-myristoyltransferase as a drug target in Leishmania donovani. ACS Infect Dis. 5: 111–122. https://www.ncbi.nlm.nih.gov/pubmed/30380837
2018
Fersing, C., Basmaciyan, L., Boudot, C., Pedron, J., Hutter, S., Cohen, A., Castera-Ducros, C., Primas, N., Laget, M., Casanova, M., Bourgeade-Delmas, S., Piednoel, M., Sournia-Saquet, A., Belle Mbou, V., Courtioux, B., Boutet-Robinet, E., Since, M., Milne, R., Wyllie, S., Fairlamb, A. H., Valentin, A., Rathelot, P., Verhaeghe, P., Vanelle, P., Azas, N. (2018) Non-genotoxic 3-nitroimidazo[1,2-a]pyridines are NTR1 substrates that display potent in vitro antileishmanial activity. ACS Med Chem Lett. 10: 34-39. https://www.ncbi.nlm.nih.gov/pubmed/30655943
Webster, L. A., Thomas, M., Urbaniak, M., Wyllie, S., Ong, H. B., Tinti, M., Fairlamb, A. H., Boesche, M., Ghidelli-Disse, S., Drewes, G. and Gilbert, I. H. (2018) Development of Chemical Proteomics for the Folateome and Analysis of the Kinetoplastid Folateome. ACS Infect Dis. 4: 1475-1486. https://www.ncbi.nlm.nih.gov/pubmed/30264983
Pedron, J., Boudot, C., Bourgeade-Delmas, S. et al. (2018) Antitrypanosomatid Pharmacomodulation at Position 3 of the 8-Nitroquinolin-2(1H)-one Scaffold Using Palladium-Catalysed Cross-Coupling Reactions. ChemMedChem. 13: 2217-2228. https://www.ncbi.nlm.nih.gov/pubmed/30221468
Wall, R.J., Rico, E., Lukac, I., Zuccotto, F., Elg, S., Gilbert, I. H., Freund, Y., Alley, M. R. K., Field, M. C., Wyllie, S. and Horn D. (2018) Clinical and veterinary trypanocidal benzoxaboroles target CPSF3. PNAS 115: 9616-9621. https://www.ncbi.nlm.nih.gov/pubmed/30185555
Fersing, C., Boudot, C., Pedron, J. et al. (2018) 8-Aryl-6-chloro-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridines as potent antitrypanosomatid molecules bioactivated by type I nitroreductases. Eur J Med Chem. 157:115-126. https://www.ncbi.nlm.nih.gov/pubmed/30092366
Wyllie, S. Thomas, M., Patterson, S. et al. (2018) Cyclin-dependent kinase 12, a novel drug target for visceral leishmaniasis. Nature 560:192-197. https://www.ncbi.nlm.nih.gov/pubmed/30046105
Pedron, J., Boudot, C., Hutter, S. et al. (2018) Novel 8-nitroquinolin-2(1H)-ones as NTR-bioactivated antikinetoplastid molecules: Synthesis, electrochemical and SAR study. Eur J Med Chem. 155:135-152. https://www.ncbi.nlm.nih.gov/pubmed/29885575
Wall, R. J., Moniz, S., Thomas, M. G., Norval, S., Ko, E. J., Marco, M., Miles, T. J., Gilbert, I. H., Horn, D., Fairlamb, A. H. and Wyllie S. (2018) Anti-trypanosomal 8-hydroxy naphthyridines are chelators of divalent transition metals. Antimicrob Agents Chemother. 62. pii: e00235-18. https://www.ncbi.nlm.nih.gov/pubmed/29844044
2017
Torrie, L. S, Brand, S. Robinson, D. A. et al. (2017) Chemical Validation of Methionyl-tRNA Synthetase as a Druggable Target in Leishmania donovani. ACS Infect Dis. 3: 718-727. https://www.ncbi.nlm.nih.gov/pubmed/28967262
Field, M. C., Horn, D., Fairlamb, A. H., Ferguson, M. A. J., Gray, D. W., Read, K. D., De Rycker, M., Torrie, L. S., Wyatt, P. G., Wyllie, S. and Gilbert, I. H. (2016) Antitrypanosomatid drug discovery: An ongoing challenge and a continuing need. Nature Rev. Microbiol. 15, 217-231. https://www.ncbi.nlm.nih.gov/pubmed/28579611
2016
Wyllie, S., Norval, S., Roberts, A. J., Patterson, S., Foth, B. J., Berriman, M., Read, K. D. and Fairlamb, A. H. (2016) Activation of bicyclic nitro-drugs by a novel nitroreductase (NTR2) in Leishmania. PLoS Pathog. e1005971. https://www.ncbi.nlm.nih.gov/pubmed/27812217
Mode of Action Group 