title: Synthesis, Molecular Structure, DNA/Protein Binding, Cytotoxicity, Apoptosis, Reactive Oxygen Species, and Mitochondrial Membrane Potential of Dibenzoxanthenes Derivatives.
abstract: Two dibenzoxanthene isomers 3 and 4 were synthesized and characterized. The crystal structures of the two compounds were solved by single-crystal X-ray diffraction. Binding of two compounds with calf thymus DNA (CT DNA) and BSA (bovine serum albumin) has been thoroughly investigated by UV-Vis and fluorescence spectroscopy. The DNA-binding constants were determined to be 2.51 (± 0.09) × 10(3) for compound 3 and 4.55 (± 0.10) × 10(3) for compound 4. Two compounds can cleave pBR322 DNA upon irradiation. Significant nuclear damages of BEL-7402 cells were observed with compound treatment in a comet assay. The cytotoxicity in vitro was investigated by MTT method. These compounds have been found to induce nuclear condensation and fragmentation in BEL-7402 cells. The two compounds can enhance intracellular reactive oxygen species and decrease the mitochondrial membrane potential. The compounds activated caspase-3 and caspase-7, down-regulated the expression levels of anti-apoptotic protein Bcl-2, and up-regulated the expression levels of pro-apoptotic protein Bax. These compounds induce apoptosis of BEL-7402 cells through an ROS-mediated mitochondrial dysfunction pathway.
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors.forename: Bing-Jie
authors.initials: BJ
authors.lastname: Han
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China. lyjche@163.com.
authors.forename: Yun-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China. wxzqq1234@163.com.
authors.forename: Xiu-Zhen
authors.initials: XZ
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002417:Cattle; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008958:Models, Molecular; D015394:Molecular Structure; D010957:Plasmids / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014966:Xanthenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D011506:Proteins; D017382:Reactive Oxygen Species; D014966:Xanthenes; C011759:dibenzoxanthenes; D004247:DNA; C427203:calf thymus DNA
keywords: Apoptosis; Bibenzoxanthene; Comet assay; Cytotoxicity; DNA binding