Synthesis, DNA interaction, and cytotoxic activity of a novel proflavine-dithiazolidinone pharmacophore.

Five novel proflavine-dithiazolidinone derivatives 4a-4e have been designed and synthesized by the reaction of dialkyl acridin-3,6-diyl dithioureas 3a-3e with methyl bromoacetate. The binding affinity of dithiazolidinone hydrochlorides 5a-5e with calf thymus DNA and plasmid (pUC19) DNA was investigated by a variety of spectroscopic techniques including UV-vis, fluorescence, and CD spectroscopy. The effects of 5a-5e on the thermal denaturation profiles of calf thymus DNA were also studied.

Involvement of glutathione in the cytotoxicity of 9-isothiocyanatoacridine.

Isothiocyanates (ITCs) are phytochemicals with promising cancer-preventive potential. To elucidate the mechanism of cytotoxicity of ITCs, their accumulation by cells and the role of intracellular glutathione, fluorescent 9-isothiocyanatoacridine (AcITC) was synthesized. The kinetic parameters for the reactions of AcITC with thiols were estimated and the influence of AcITC on human chronic myeloid leukemia cell line (K562) in regard to intracellular glutathione was studied.