2. Academic Validation
  3. Synthesis of five libraries of 6,5-fused heterocycles to establish the importance of the heterocyclic core for antiplasmodial activity

Synthesis of five libraries of 6,5-fused heterocycles to establish the importance of the heterocyclic core for antiplasmodial activity

  • Bioorg Med Chem. 2018 Nov 15;26(21):5730-5741. doi: 10.1016/j.bmc.2018.10.029.
Leon Jacobs 1,  Carmen de Kock 2,  Dale Taylor 2,  Stephen C Pelly 3,  Margaret A L Blackie 4
Affiliations

Affiliations

  • 1 Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa.
  • 2 Department of Pharmacology, University of Cape Town, Private Bag X2, Rondebosch, Cape Town 7700, South Africa.
  • 3 Department of Chemistry, Emory University, Atlanta, GA, USA.
  • 4 Department of Chemistry and Polymer Science, Stellenbosch University, Private Bag X1, Matieland, 7602, South Africa. Electronic address: mblackie@sun.ac.za.
PMID: 30391094 DOI: 10.1016/j.bmc.2018.10.029
Abstract

Research has indicated that N-myristoyl transferase, an Enzyme that catalyzes the addition of a myristate group to the N-terminal glycine residues of proteins, is involved in the myristoylation of more than 100 proteins. Genetic knockdown of the Enzyme proved detrimental for the viability of the Parasite P. knowlesi. A crystal structure of P. vivax N-myristoyl transferase (pvNMT), containing a 3-methyl benzofuran ligand has made it possible to assess key amino acid residue-ligand interactions. We synthesized five libraries of 6,5-fused heterocycles to establish the importance of the heterocycles as core scaffolds, as well as introduced various aromatic amides and esters to determine which carbonylic group affects the potency of each heterocyclic antiplasmodial agent.

Keywords

Antiplasmodial; Heterocycles; Malaria; NF54; pfNMT inhibitors.

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