Synthesis, DNA Interaction, and Cytotoxic Activity of a Novel Proflavine−Dithiazolidinone Pharmacophore

• DOI: 10.1021/bc060168v
• Publication Date: 2006-11-07T12:58:18Z
• Authors: Ladislav Janovec; Danica Sabolová; Mária Kožurková; Helena Paulíková; Pavol Kristian; Ján Ungvarský; Erika Moravčíková; Mária Bajdichová; Dušan Podhradský; Ján Imrich
• Keywords: HeLa; pUC19; Proflavine

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 dithiazolidinone hydrochlorides 5a−5e calf thymus DNA plasmid (pUC19) was investigated a variety spectroscopic techniques including UV−vis, fluorescence, CD spectroscopy. effects on thermal denaturation profiles were also studied. From spectrophotometric spectrofluorimetric titrations, constants for pUC19 DNA−drug complexes determined (K = 6.2−2.2 × 104 M-1). In vitro cytotoxic activities compounds toward murine leukemia cell line L1210 human uterus carcinoma HeLa cells examined. 2',2' '-[(Acridin-3,6-diyl)diimino]-3',3' '-dipropyl-1,3-dithiazolidin-4-one hydrochloride (5b) showed highest activity against these IC50 values 6.3 μM 12.9 over course 72 h.