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

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 (IC50: 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.