Molecular hybrids of (2R, 3S)-N-benzoyl-3-phenylisoserine with antimalarial scaffolds design, synthesis and biological evaluation for antitumoural and antiplasmodial activity

Abstract

Alpha-hydroxy-(3-amino acids, isoserines, are important members of the (3-amino acids family because many of them act as potent enzyme inhibitors and as crucial building blocks for compounds of biological and medicinal importance. One such privileged amino acid· is {2R,3S}N-benzoyl-3-phenylisoserine, one of the two main structural motifs in the anticancer drug paclitaxel (Taxol®). This amino acid has been shown to play an essential role in the antimicrotubular activity of paclitaxel, a prototypical taxane. Taxanes are clinically used as antineoplastics. Previous independent research studies revealed that they also possess strong antimalarial efficacy. Structure activity relationship studies show that modifications of the {2R,3S}N-benzoyl-3~phenylisoserine moiety results in improvement of both the antineoplastic and antiplasmodial activities of taxanes.