Antiproliferative Activity of β-Hydroxy-β-Arylalkanoic Acids

Article describes the synthesis of fifteen β-hydroxy-β-arylalkanoic acids by Reformatsky reaction using the 1-ethoxyethyl-2-bromoalkanoates, aromatic or cycloalkyl ketones or aromatic aldehydes. The short survey of previously reported synthetic procedures for title compounds, is given. The majority of obtained compounds exert antiproliferative activity in vitro toward human: HeLa, Fem-X cells, K562, and LS174 cells, having IC₅₀ values from 62.20 to 205 μM. The most active compound is 3-OH-2,2-di-Me-3-(4- biphenylyl)-butanoic acid, having the IC₅₀ value 62.20 μM toward HeLa cells. Seven examined compounds did not affect proliferation of healthy human blood peripheral mononuclear cells (PBMC and PBMC+ PHA), IC₅₀ > 300 μM. The preliminary QSAR results show that estimated lipophilicity of compounds influences their antiproliferative activity in the first place. The ability of dehydration, and the spatial arrangement of hydrophobic portion, HBD and HBA in molecules are has almost equal importance as lipophilicity.