From DC18 to MR07: A Metabolically Stable 4,4'-Oxybisbenzoyl Amide as a Low-Nanomolar Growth Inhibitor of P. falciparum.

ABSTRACT: To improve the metabolic stability of a 4,4'-oxybisbenzoyl-based novel and potent (nanomolar-range IC₅₀ ) antiplasmodial agent previously described by us, in silico-guided structure-activity relationship (SAR) campaigns have been conducted to substitute its peptide decorations with more metabolically stable residues. The effects of the various structural modifications were then correlated with the antiplasmodial activity in vitro in phenotypic assays. Among the several derivatives synthetized and compared with the 3D-pharmacophoric map of the original lead, a novel compound, characterized by a western tert-butyl glycine residue and an eastern 1S,2S-aminoacyclohexanol, showed low-nanomolar-range antiplasmodial activity, no signs of cross-resistance and, most importantly, 47-fold

SUBMITTER: Bassanini I 

PROVIDER: S-EPMC9827966 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature