Medicinal Chemistry Group

Publications

 A selection of our publications by research area.


Malaria

4-Aminoquinolines

Candidate Selection and Preclinical Evaluation of N - tert -Butyl Isoquine (GSK369796), An Affordable and Effective 4-Aminoquinoline Antimalarial for the 21st Century (Journal article)

O’Neill, P. M., Park, B. K., Shone, A. E., Maggs, J. L., Roberts, P., Stocks, P. A., . . . Ward, S. A. (2009). Candidate Selection and Preclinical Evaluation of N - tert -Butyl Isoquine (GSK369796), An Affordable and Effective 4-Aminoquinoline Antimalarial for the 21st Century. Journal of Medicinal Chemistry, 52(5), 1408-1415. doi:10.1021/jm8012618

DOI: 10.1021/jm8012618

Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. identification of a suitable "back-up" compound for N-tert-butyl isoquine (Journal article)

O'Neill, P. M., Shone, A. E., Stanford, D., Nixon, G., Asadollahy, E., Park, B. K., . . . Ward, S. A. (2009). Synthesis, antimalarial activity, and preclinical pharmacology of a novel series of 4'-fluoro and 4'-chloro analogues of amodiaquine. identification of a suitable "back-up" compound for N-tert-butyl isoquine. Journal of Medicinal Chemistry, 52(7), 1828-1844. doi:10.1021/jm8012757

DOI: 10.1021/jm8012757

Novel Peroxide Antimalarials

Identification of a 1,2,4,5-tetraoxane antimalarial drug-development candidate (RKA 182) with superior properties to the semisynthetic artemisinins (Journal article)

O'Neill, P. M., Amewu, R. K., Nixon, G. L., ElGarah, F. B., Mungthin, M., Chadwick, J., . . . Ward, S. A. (2010). Identification of a 1,2,4,5-tetraoxane antimalarial drug-development candidate (RKA 182) with superior properties to the semisynthetic artemisinins. Angewandte Chemie - International Edition, 49(33), 5693-5697. doi:10.1002/anie.201001026

DOI: 10.1002/anie.201001026

Second generation analogues of RKA182: synthetic tetraoxanes with outstanding in vitro and in vivo antimalarial activities (Journal article)

Marti, F., Chadwick, J., Amewu, R. K., Burrell-Saward, H., Srivastava, A., Ward, S. A., . . . O'Neill, P. M. (2011). Second generation analogues of RKA182: synthetic tetraoxanes with outstanding in vitro and in vivo antimalarial activities. MedChemComm, 2(7), 661. doi:10.1039/c1md00102g

DOI: 10.1039/c1md00102g

Antimalarial Mannoxanes: Hybrid Antimalarial Drugs with Outstanding Oral Activity Profiles and A Potential Dual Mechanism of Action (Journal article)

Chadwick, J., Amewu, R. K., Marti, F., Garah, F. B. -E., Sharma, R., Berry, N. G., . . . O'Neill, P. M. (2011). Antimalarial Mannoxanes: Hybrid Antimalarial Drugs with Outstanding Oral Activity Profiles and A Potential Dual Mechanism of Action. ChemMedChem, 6(8), 1357-1361. doi:10.1002/cmdc.201100196

DOI: 10.1002/cmdc.201100196

Targeting PfNDH2

Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:Quinone oxidoreductase (PfNDH2) (Journal article)

Pidathala, C., Amewu, R., Pacorel, B., Nixon, G. L., Gibbons, P., Hong, W. D., . . . O'Neill, P. M. (2012). Identification, design and biological evaluation of bisaryl quinolones targeting Plasmodium falciparum type II NADH:Quinone oxidoreductase (PfNDH2). Journal of Medicinal Chemistry, 55(5), 1831-1843. doi:10.1021/jm201179h

DOI: 10.1021/jm201179h

Identification of novel antimalarial chemotypes via chemoinformatic compound selection methods for a high-throughput screening program against the novel malarial target, PfNDH2: Increasing hit rate via virtual screening methods (Journal article)

Sharma, R., Lawrenson, A. S., Fisher, N. E., Warman, A. J., Shone, A. E., Hill, A., . . . Berry, N. G. (2012). Identification of novel antimalarial chemotypes via chemoinformatic compound selection methods for a high-throughput screening program against the novel malarial target, PfNDH2: Increasing hit rate via virtual screening methods. Journal of Medicinal Chemistry, 55(7), 3144-3154. doi:10.1021/jm3001482

DOI: 10.1021/jm3001482

Identification, design and biological evaluation of heterocyclic quinolones targeting plasmodium falciparum Type II NADH:Quinone oxidoreductase (PfNDH2) (Journal article)

Leung, S. C., Gibbons, P., Amewu, R., Nixon, G. L., Pidathala, C., Hong, W. D., . . . O'Neill, P. M. (2012). Identification, design and biological evaluation of heterocyclic quinolones targeting plasmodium falciparum Type II NADH:Quinone oxidoreductase (PfNDH2). Journal of Medicinal Chemistry, 55(5), 1844-1857. doi:10.1021/jm201184h

DOI: 10.1021/jm201184h

Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria(Journal article)

Biagini, G. A., Fisher, N., Shone, A. E., Mubaraki, M. A., Srivastava, A., Hill, A., . . . Ward, S. A. (2012). Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria. Proceedings of the National Academy of Sciences of the United States of America, 109(21), 8298-8303. doi:10.1073/pnas.1205651109

DOI: 10.1073/pnas.1205651109 

New Quinolone Inhibitors Targeting the Cytochrome bc1 Complex of Plasmodium falciparum

Antimalarial 4(1H)-pyridones bind to the Q(i) site of cytochrome bc(1) (Journal article)

Capper, M. J., O'Neill, P. M., Fisher, N., Strange, R. W., Moss, D., Ward, S. A., . . . Antonyuk, S. V. (2015). Antimalarial 4(1H)-pyridones bind to the Q(i) site of cytochrome bc(1). PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 112(3), 755-760. doi:10.1073/pnas.1416611112

DOI: 10.1073/pnas.1416611112

MEP Pathway

Plasmodium IspD (2-C-Methyl- d -erythritol 4-Phosphate Cytidyltransferase), an Essential and Druggable Antimalarial Target (Journal article)

Imlay, L. S., Armstrong, C. M., Masters, M. C., Li, T., Price, K. E., Edwards, R. L., . . . Odom, A. R. (2016). Plasmodium IspD (2-C-Methyl- d -erythritol 4-Phosphate Cytidyltransferase), an Essential and Druggable Antimalarial Target. ACS Infectious Diseases, 1(4), 157-167. doi:10.1021/id500047s

DOI: 10.1021/id500047s


Chemical Biology

Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions (Journal article)

Ismail, H. M., O'Neill, P. M., Hong, D. W., Finn, R. D., Henderson, C. J., Wright, A. T., . . . Paine, M. J. I. (2013). Pyrethroid activity-based probes for profiling cytochrome P450 activities associated with insecticide interactions. Proceedings of the National Academy of Sciences, 110(49), 19766-19771. doi:10.1073/pnas.1320185110

DOI: 10.1073/pnas.1320185110


Cyclophilins as Drug Targets

Small Molecule Inhibitors of Cyclophilin D to Protect Mitochondrial Function as a Potential Treatment for Acute Pancreatitis (Journal article)

Shore, E. R., Awais, M., Kershaw, N. M., Gibson, R. R., Pandalaneni, S., Latawiec, D., . . . Sutton, R. (2016). Small Molecule Inhibitors of Cyclophilin D to Protect Mitochondrial Function as a Potential Treatment for Acute Pancreatitis. Journal of Medicinal Chemistry, 59(6), 2596-2611. doi:10.1021/acs.jmedchem.5b01801

DOI: 10.1021/acs.jmedchem.5b01801