title: Cytotoxic activity of proflavine diureas: synthesis, antitumor, evaluation and DNA binding properties of 1',1''-(acridin-3,6-diyl)-3',3''-dialkyldiureas.
abstract: The synthesis of novel 1',1''-(acridin-3,6-diyl)-3',3''-dialkyldiureas was reported. Their biological activity to inhibit cell proliferation was assessed by a MTT assay on two cell lines, HeLa and HCT-116, at micromolar concentration. 1',1''-(Acridin-3,6-diyl)-3',3''-dihexyldiurea hydrochloride was active on a HCT-116 cell line with an IC(50) value of 3.1 microM. The interaction of these compounds with calf thymus DNA was investigated by a variety of spectroscopic techniques including UV-vis, fluorescence and CD spectroscopy. From spectrofluorimetric titrations, binding constants for the DNA-drug complexes were determined (K=0.9-4.2x10(5) M(-1)). Antiproliferative activity of synthesized derivatives might be related to their intercalation into DNA.
authors.affiliation: Department of Biochemistry, Institute of Chemistry, Faculty of Science, P. J. Safárik University, SK-04167 Kosice, Slovakia.
authors.forename: Mária
authors.initials: M
authors.lastname: Kozurková
authors.forename: Danica
authors.initials: D
authors.lastname: Sabolová
authors.forename: Ladislav
authors.initials: L
authors.lastname: Janovec
authors.forename: Jaromír
authors.initials: J
authors.lastname: Mikes
authors.forename: Ján
authors.initials: J
authors.lastname: Koval'
authors.forename: Ján
authors.initials: J
authors.lastname: Ungvarský
authors.forename: Miroslava
authors.initials: M
authors.lastname: Stefanisinová
authors.forename: Peter
authors.initials: P
authors.lastname: Fedorocko
authors.forename: Pavol
authors.initials: P
authors.lastname: Kristian
authors.forename: Ján
authors.initials: J
authors.lastname: Imrich
mesh_terms: D000166:Acridines / Q000737:chemistry*; D000478:Alkylation; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry* / Q000235:genetics; D006801:Humans; D015394:Molecular Structure; D010777:Photochemistry; D011370:Proflavine / Q000737:chemistry*; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D017186:Titrimetry; D014508:Urea / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D014508:Urea; D004247:DNA; D011370:Proflavine