title: Microwave-assisted synthesis of phenanthroimidazole derivatives as stabilizer of c-myc G-quadruplex DNA.
abstract: c-myc G-quadruplex DNA, which plays a central role in tumor progression and resistance, has been extensively investigated as potential target of antitumor drugs. In this paper, a series of phenanthroimidazole derives have been synthesized under irradiation of microwave in yields of 51–80%. The antitumor activity of these compounds against various tumor cells has been evaluated, and the results show that these compounds exhibit great inhibition to MDA-MB-231, MCF-7 and Hela cells, especially 5 inhibit the growth of MDA-MB-231 cells with IC50 about 3.6 lM. The further studies show that 5 can bind and stabilize c-myc G4 DNA in p–p stacking mode, which confirmed by the hypochromise in the electronic spectra of 5 with the increasing of c-myc G4 DNA. When dealt with 5, the strength of CD signal attributed to c-myc G4 DNA is decreased and the FRET melting point of c-myc G4 DNA is increased. Moreover, the molecule docking calculation was conducted to show that 5 suitably stack onto the 50 G-quartet surface, and parallels to the surfaces of the G5 and G-quartet consisting of G7, G11, G16, and G20. As a result, the replication of c-myc oligomers is blocked by 5. In a word, this type of phenanthroimidazole derives can act as potential inhibitor against breast cancer cells by binding and stabilizing c-myc G4 DNA through p–p stacking.
authors.forename: Siyan
authors.initials: S
authors.lastname: Liao
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Xicheng
authors.initials: X
authors.lastname: Wang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Mei
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002942:Circular Dichroism; D054856:G-Quadruplexes; D006367:HeLa Cells; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism / Q000633:toxicity; D061986:MCF-7 Cells; D008872:Microwaves; D062105:Molecular Docking Simulation; D009690:Nucleic Acid Conformation; D009691:Nucleic Acid Denaturation; D010616:Phenanthrenes / Q000737:chemistry; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D007093:Imidazoles; D010616:Phenanthrenes; D016271:Proto-Oncogene Proteins c-myc