One-pot synthesis and cytotoxicity studies of new Mannich base derivatives of polyether antibiotic—Lasalocid acid

Abstract Seven Mannich base derivatives of polyether antibiotic Lasalocid acid ( 2a – 2g ) were synthesized and screened for their antiproliferative activity against various human cancer cell lines. A novel chemoselective one-pot synthesis of these Mannich bases was developed. Compounds 2a – 2c and 2g with sterically smaller dialkylamine substituent, displayed potent antiproliferative activity (IC 50 : 3.2–7.3 μM), and demonstrated higher than twofold selectivity for specific type of cancer. The nature of Mannich base substituent on C-2 atom at the aromatic ring may be critical in the search for selectivity towards a particular cancer cell.