Synthesis, Molecular Structure, DNA/Protein Binding, Cytotoxicity, Apoptosis, Reactive Oxygen Species, and Mitochondrial Membrane Potential of Dibenzoxanthenes Derivatives

Overview

Journal J Membr Biol

Date 2015 Sep 25

PMID 26400779

Authors

Hui-Hui Yang

Bing-Jie Han

Wei Li

Yun-Jun Liu

Xiu-Zhen Wang

Affiliations

Soon will be listed here.

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.

References

Satyanarayana S, Dabrowiak J, Chaires J . Tris(phenanthroline)ruthenium(II) enantiomer interactions with DNA: mode and specificity of binding. Biochemistry. 1993; 32(10):2573-84. DOI: 10.1021/bi00061a015. View

SAINT-RUF G, Poupelin J . The effect of dibenzoxanthenes on the paralyzing action of zoxazolamine. Naturwissenschaften. 1975; 62(12):584-5. DOI: 10.1007/BF01166986. View

Hecht S . Bleomycin: new perspectives on the mechanism of action. J Nat Prod. 2000; 63(1):158-68. DOI: 10.1021/np990549f. View

Cory S, Huang D, Adams J . The Bcl-2 family: roles in cell survival and oncogenesis. Oncogene. 2003; 22(53):8590-607. DOI: 10.1038/sj.onc.1207102. View

Sathyadevi P, Krishnamoorthy P, Bhuvanesh N, Kalaiselvi P, Vijaya Padma V, Dharmaraj N . Organometallic ruthenium(II) complexes: synthesis, structure and influence of substitution at azomethine carbon towards DNA/BSA binding, radical scavenging and cytotoxicity. Eur J Med Chem. 2012; 55:420-31. DOI: 10.1016/j.ejmech.2012.08.001. View

Guadagno T, Ferrell Jr J . Requirement for MAPK activation for normal mitotic progression in Xenopus egg extracts. Science. 1998; 282(5392):1312-5. DOI: 10.1126/science.282.5392.1312. View

Li W, Jiang G, Yao J, Wang X, Wang J, Han B . Ruthenium(II) complexes: DNA-binding, cytotoxicity, apoptosis, cellular localization, cell cycle arrest, reactive oxygen species, mitochondrial membrane potential and western blot analysis. J Photochem Photobiol B. 2014; 140:94-104. DOI: 10.1016/j.jphotobiol.2014.07.011. View

Kelly J, Murphy M, McConnell D, OhUigin C . A comparative study of the interaction of 5,10,15,20-tetrakis (N-methylpyridinium-4-yl)porphyrin and its zinc complex with DNA using fluorescence spectroscopy and topoisomerisation. Nucleic Acids Res. 1985; 13(1):167-84. PMC: 340982. DOI: 10.1093/nar/13.1.167. View

Paitandi R, Gupta R, Singh R, Sharma G, Koch B, Pandey D . Interaction of ferrocene appended Ru(II), Rh(III) and Ir(III) dipyrrinato complexes with DNA/protein, molecular docking and antitumor activity. Eur J Med Chem. 2014; 84:17-29. DOI: 10.1016/j.ejmech.2014.06.052. View

10.

Senthil Raja D, Ramachandran E, Bhuvanesh N, Natarajan K . Synthesis, structure and in vitro pharmacological evaluation of a novel 2-oxo-1,2-dihydroquinoline-3-carbaldehyde (2'-methylbenzoyl) hydrazone bridged copper(II) coordination polymer. Eur J Med Chem. 2013; 64:148-59. DOI: 10.1016/j.ejmech.2013.03.040. View

11.

Hafez H, Hegab M, Ahmed-Farag I, el-Gazzar A . A facile regioselective synthesis of novel spiro-thioxanthene and spiro-xanthene-9',2-[1,3,4]thiadiazole derivatives as potential analgesic and anti-inflammatory agents. Bioorg Med Chem Lett. 2008; 18(16):4538-43. DOI: 10.1016/j.bmcl.2008.07.042. View

12.

Wang X, Jiang G, Xie Y, Liu Y . Synthesis, molecular structure, DNA interaction and antioxidant activity of novel naphthoxazole compound. Spectrochim Acta A Mol Biomol Spectrosc. 2013; 118:448-53. DOI: 10.1016/j.saa.2013.09.028. View

13.

Chaires J, Dattagupta N, Crothers D . Studies on interaction of anthracycline antibiotics and deoxyribonucleic acid: equilibrium binding studies on interaction of daunomycin with deoxyribonucleic acid. Biochemistry. 1982; 21(17):3933-40. DOI: 10.1021/bi00260a005. View

14.

Wolfe A, Shimer Jr G, Meehan T . Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochemistry. 1987; 26(20):6392-6. DOI: 10.1021/bi00394a013. View

15.

Watson J, Hill R, Yaffe P, Greenshields A, Walsh M, Lee P . Curcumin causes superoxide anion production and p53-independent apoptosis in human colon cancer cells. Cancer Lett. 2010; 297(1):1-8. DOI: 10.1016/j.canlet.2010.04.018. View

16.

Collins A, Oscoz A, Brunborg G, Gaivao I, Giovannelli L, Kruszewski M . The comet assay: topical issues. Mutagenesis. 2008; 23(3):143-51. DOI: 10.1093/mutage/gem051. View

17.

Watson J, Hill R, Lee P, Giacomantonio C, Hoskin D . Curcumin induces apoptosis in HCT-116 human colon cancer cells in a p21-independent manner. Exp Mol Pathol. 2008; 84(3):230-3. DOI: 10.1016/j.yexmp.2008.02.002. View

18.

Wang X, Yang B, Lin G, Xie Y, Huang H, Liu Y . Cytotoxicity, cell cycle arrest, antioxidant activity and interaction of dibenzoxanthenes derivatives with DNA. DNA Cell Biol. 2012; 31(9):1468-74. DOI: 10.1089/dna.2012.1726. View

19.

Wasson G, McKelvey-Martin V, Downes C . The use of the comet assay in the study of human nutrition and cancer. Mutagenesis. 2008; 23(3):153-62. DOI: 10.1093/mutage/gen003. View

20.

Waring M . Complex formation between ethidium bromide and nucleic acids. J Mol Biol. 1965; 13(1):269-82. DOI: 10.1016/s0022-2836(65)80096-1. View