Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase

Victor Goncalves (1) , James A. Brannigan (2) , Alice Laporte (1) , Andrew S. Bell (1) , Shirley M. Roberts (2) , Anthony J. Wilkinson (2) , Robin J. Leatherbarrow (1) , Edward W. Tate (1)

1 Department of Chemistry [Imperial College London]
2 Structural Biology Laboratory, Department of Chemistry, University of York

The parasite Plasmodium vivax is the most widely distributed cause of recurring malaria. N-Myristoyltransferase (NMT), an enzyme that catalyses the covalent attachment of myristate to the N-terminal glycine of substrate proteins, has been described as a potential target for the treatment of this disease. Herein, we report the synthesis and the structure-guided optimization of a series of quinolines with balanced activity against both Plasmodium vivax and Plasmodium falciparum N-myristoyltransferase (NMT).

Mots clés: potential-drug target; myristoyl-coa; selective inhibitors; vivax malaria; discovery; design; ligand; leishmaniasis; falciparum; parasites

Domaines: Sciences du Vivant [q-bio]; Biochimie, Biologie Moléculaire

Victor Goncalves, James A. Brannigan, Alice Laporte, Andrew S. Bell, Shirley M. Roberts, et al.. Structure-guided optimization of quinoline inhibitors of Plasmodium N-myristoyltransferase. MedChemComm, 2017, 8 (1), pp.191 - 197. ⟨10.1039/C6MD00531D⟩. ⟨hal-01496799⟩