Antimutagenicity of phenothiazine-metal co-ordination complexes in chemically induced mutagenesis

Phenothiazines are heterocyclic organic compounds in which nitrogen and sulfur are incorporated in the tricyclic system, and are known to have antimutagenic activity by shielding DNA-base pairs. Inorganic metals have also been intensively studied for DNA-adduct formation as potential anticancer agents. Phenothiazine, promethazine, promazine and chlorpromazine were complexed either with copper, palladium or gold. The antimutagenicity of twelve phenothiazine-metal complexes, four phenothiazines and three inorganic metals was examined on Salmonella typhimurium TA98 strain treated with a strain-specific, direct-acting mutagen, 4-nitro-o-phenylene-diamine, and the ligand-DNA interaction was analyzed by ultraviolet (UV) spectrophotometry. Phenothiazine-metal co-ordination complexes generally increased their antimutagenic activity, compared to their parent compounds, and the enhanced antimutagenicity was attributed to their interaction with DNA as evidenced by the UV spectra.