Microwave-assisted synthesis of phenanthroimidazole derivatives as stabilizer of c-myc G-quadruplex DNA |
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| Affiliation: | 1. Department of Chemistry, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou 510182, PR China;2. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China;3. The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510006, PR China;1. Laboratory of Chemical Design of Bionanomaterials, Chemistry Department, M.V. Lomonosov Moscow State University, Russian Federation;2. Center for Nanotechnology in Drug Delivery and Division of Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA;3. R.G. Derzhavin Tambov State University, Russian Federation;4. National University of Science and Technology MISiS, Leninsky Ave, 4, 119049 Moscow, Russian Federation;1. Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China;2. Lab of Molecular Immunology, Virus Inspection Department, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China |
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| 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 μM. The further studies show that 5 can bind and stabilize c-myc G4 DNA in π–π 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 5′ 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 π–π stacking. |
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| Keywords: | Phenanthroimidazole derives π–π stacking Molecular docking |
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