Synthesis of five libraries of 6, 5-fused heterocycles to establish the importance of the heterocyclic core for antiplasmodial activity. Issue 21 (15th November 2018)

• Record Type: Journal Article
• Authors: Jacobs, Leon; de Kock, Carmen; Taylor, Dale; Pelly, Stephen C.; Blackie, Margaret A.L.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 26:Issue 21(2018)
• Page Start: 5730
• Page End: 5741
• Publication Date: 2018-11-15
• Subjects: Heterocycles -- pfNMT inhibitors -- Antiplasmodial -- NF54 -- Malaria; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2018.10.029
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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.