title: Microwave-assisted synthesis of arene ruthenium(II) complexes [(η⁶-RC₆H₅)Ru(m-MOPIP)Cl]Cl (R = -H and -CH₃) as groove binder to c-myc G4 DNA.
abstract: Two arene Ru(II) complexes coordinated by 2-(3-methoxyphenyl)imidazole[4,5-f][1,10]phenanthroline, [(η(6)-RC6H5)Ru(m-MOPIP)Cl]Cl (R = H, ; R = CH3, 2), have been prepared under microwave irradiation; the crystal structure of 2 exhibits a typical "piano stool" conformation, with bond angles for N1-Ru1-Cl1 86.02 (14)° and N2-Ru1-Cl1 84.51 (14)°. The Ru-C distance for the Ru atom bound to the benzene ring is about 0.2178(8) nm, and the average Ru-N distance for Ru atom to the two chelating N atoms is about 0.2092(4) nm. The evaluation of in vitro anticancer activities revealed that these synthetic Ru(II) complexes selectively inhibited the growth of HepG2 hepatocellular carcinoma cells, with low cytotoxicity toward LO2 human normal liver cells. The results demonstrated that the complexes exhibited great selectivity between human cancer and normal cells by comparing with the ligand m-MOPIP. Furthermore, complexes 1 and 2 could bind to c-myc G4 DNA in groove binding mode in promising affinity, and the insertion of the methyl groups in the arene ligand contributed to strengthen the binding affinity. This was also confirmed by molecular docking calculation and (1)H NMR analysis which showed that both 1 and 2 can bind in the loop constructed by A6-G9 and G21-A25 base pairs in c-myc G4 DNA to block the replication of c-myc oligomer. Taken together, these results suggest that arene Ru(II) complexes display application potential as small molecule inhibitors of c-myc G4 DNA.
authors.affiliation: School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, P.R. China. wenjiemei@126.com.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Tianfeng
authors.initials: T
authors.lastname: Chen
authors.forename: Zhao
authors.initials: Z
authors.lastname: Zhang
authors.forename: Siyan
authors.initials: S
authors.lastname: Liao
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Wu
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Wenjie
authors.initials: W
authors.lastname: Mei
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Chen
authors.forename: Weili
authors.initials: W
authors.lastname: Wu
authors.forename: Lingli
authors.initials: L
authors.lastname: Zeng
authors.forename: Wenjie
authors.initials: W
authors.lastname: Zheng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D001554:Benzene / Q000737:chemistry; D002151:Calorimetry; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D008099:Liver / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008872:Microwaves; D008958:Models, Molecular; D015394:Molecular Structure; D010618:Phenanthrolines / Q000737:chemistry; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D011487:Protein Conformation; D012428:Ruthenium / Q000737:chemistry*; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D008024:Ligands; D010618:Phenanthrolines; D012428:Ruthenium; D004247:DNA; D001554:Benzene