A Chelating Agent Possessing Cytotoxicity and Antimicrobial Activity: 7-morpholinomethyl-8-hydroxyquinoline

7-Morpholinomethyl-8-hydroxyquinoline (MO-8HQ), which like 8-hydroxyquinoline (8HQ) readily forms a chelate, was synthesized and found to possess cytotoxicity and antimicrobial activity. Both 8HQ and MO-8HQ were cytotoxic to human carcinoma cell lines at micromolar concentrations. MO-8HQ also inhibited DNA synthesis of tumor cells at micromolar concentrations, suggesting that MO-8HQ might chelate metals necessary for the enzymatic catalysis of DNA biosynthesis. MO-8HQ was more active against gram positive bacteria than gram negative bacteria and its potency correlated with iron chelation. An "unsaturated" chelate with a MO-8HQ to Fe ratio of 2:1 exhibited greater antibacterial activity than MO-8HQ alone. Among the organisms tested, Micrococcus flavus was most susceptible with a MIC of 3.9 microg/ml. MO-8HQ also exhibited anti-fungal activity at 7-15 microg/ml. MO-8HQ:Fe chelate markedly increased the susceptibility of Escherichia coli to deoxycholate. Addition of Ca2+ or Mg2+ reversed the sensitivity of bacteria to deoxycholate as well as to rifampicin. It is suggested that MO-8HQ exerts its biological activity as a membrane-active agent through metal ion chelation.