title: DNA binding properties and biological evaluation of dihydropyrimidinones derivatives as potential antitumor agents.
abstract: The binding properties of two medicinally important dihydropyrimidinones derivatives 5-(Ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one (EMPD) and 5-(Ethoxycarbonyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one (EMCD) with calf-thymus DNA (ctDNA) were investigated by spectroscopy, viscosity, isothermal titration calorimetry (ITC) and molecular modeling techniques. Simultaneously, their biological activities were evaluated with MTT assay method. The binding constants determined with spectroscopic titration and ITC were found to be in the same order of 10(4)M(-1). According to the results of viscosity studies, fluorescence competitive binding experiment and ITC investigations, intercalative binding was evaluated as the dominant binding modes between the two compounds and ctDNA. Furthermore, the results of molecular modeling corroborated those obtained from spectroscopic, viscosimetric and ITC investigations. Evaluation of the antitumor activities of the two derivatives against different tumor cell lines proved that they exhibited significant tumor cell inhibition rate, accordingly blocking DNA transcription and replication. The present results favor the development of potential drugs related with dihydropyrimidinones derivatives in the treatment of some diseases.
authors.affiliation: School of Chemistry and Chemical Engineering, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Normal University, Xinxiang, Henan 453007, PR China.
authors.forename: Gongke
authors.initials: G
authors.lastname: Wang
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Li
authors.forename: Yaping
authors.initials: Y
authors.lastname: Gou
authors.forename: Yuhan
authors.initials: Y
authors.lastname: Chen
authors.forename: Changling
authors.initials: C
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D002417:Cattle; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004247:DNA / Q000378:metabolism*; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy; D011728:Pyridones / Q000737:chemistry* / Q000494:pharmacology*; D011744:Pyrimidinones / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C586643:5-(ethoxycarbonyl)-6-methyl-4-(4-chlorophenyl)-3,4-dihydropyrimidin-2(1H)-one; C558465:5-(ethoxycarbonyl)-6-methyl-4-phenyl-3,4-dihydropyrimidin-2(1H)-one; D000970:Antineoplastic Agents; D007364:Intercalating Agents; D011728:Pyridones; D011744:Pyrimidinones; D004247:DNA; C427203:calf thymus DNA
keywords: Antitumor activity; DNA binding; Isothermal titration calorimetry; Molecular modeling; Spectroscopy