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. From spectrophotometric and spectrofluorimetric titrations, the binding constants for the pUC19 DNA-drug complexes were determined (K = 6.2-2.2 x 104 M-1). In vitro cytotoxic activities of compounds 5a-5e toward murine leukemia cell line L1210 and human uterus carcinoma HeLa cells were also examined. 2',2' '-[(Acridin-3,6-diyl)diimino]-3',3' '-dipropyl-1,3-dithiazolidin-4-one hydrochloride (5b) showed the highest activity against these cells with IC50 values of 6.3 microM and 12.9 microM over the course of 72 h.
Janovec
Ladislav
L
Department of Organic Chemistry, Institute of Chemistry, Faculty of Science, P.J. SafArik University, Moyzesova 11, SK-04167 Kosice, Slovak Republic.
Sabolova
Danica
D
Kozurkova
Maria
M
Paulíkova
Helena
H
Kristian
Pavol
P
Ungvarský
Jan
J
Moravcíkova
Erika
E
Bajdichova
Maria
M
Podhradský
Dusan
D
Imrich
Jan
J
D000166:Acridines / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D048430:Cell Shape; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry*; D004583:Electrons; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009691:Nucleic Acid Denaturation; D010777:Photochemistry; D011370:Proflavine / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D013057:Spectrum Analysis; D013844:Thiazoles / Q000737:chemistry*; D017186:Titrimetry; D044366:Transition Temperature
D000166:Acridines; D013844:Thiazoles; D004247:DNA; C427203:calf thymus DNA; D011370:Proflavine