Optimization of the anti-cancer activity of the phosphatidylinositol-3 kinase pathway inhibitor PITENIN-1: switching thiourea with 1,2,3-triazole

Abstract

We previously reported encouraging in vitro and in vivo anti-cancer activity of N-((3-chloro-2-hydroxy-5-nitrophenyl)carbamothioyl)benzamide (termed PITENIN-1). In the current work, we describe the structure–activity relationship study of the PIT-1 series, based on the replacement of a central thiourea unit with 1,2,3-triazole, which leads to increased liver microsomal stability, drug likeness and toxicity towards cancer cells.