title: Targeting human telomeric and c-myc G-quadruplexes with alkynylplatinum(II) terpyridine complexes under molecular crowding conditions.
abstract: The interactions between alkynylplatinum(II) terpyridine complexes 1-3 and the G-quadruplex DNA, including c-myc and telomeric quadruplex DNA, are investigated both in dilute solution and under molecular crowding conditions. The UV-vis absorption spectroscopy, circular dichroism and molecular docking studies suggest that 1-3 associate with telomeric and c-myc G-quadruplexes via groove binding, and electrostatic interactions. Experimental studies indicate that under molecular crowding conditions (in the presence of 40wt% PEG 200), 1-2 show weak affinity for c-myc, while 3 still displays high affinity and selectivity for c-myc. On the other hand, 1-3 act as efficient and selective ligand for telomeric quadruplex DNA under molecular crowding conditions. The complex 3 exhibits excellent cytotoxicity against A549, K562 and SGC-7901, with IC50values that are 35.0-fold, 10.0-fold, and 12.1-fold lower than the values of cisplatin under the same conditions, respectively.
authors.affiliation: The Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education, Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an 710072, People's Republic of China.
authors.forename: Zhize
authors.initials: Z
authors.lastname: Ou
authors.affiliation: The Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education, Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an 710072, People's Republic of China.
authors.forename: Yunqing
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education, Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an 710072, People's Republic of China. Electronic address: gaoyunyan@nwpu.edu.cn.
authors.forename: Yunyan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: College of Life Science, Shaanxi Normal University, Xi'An 710062, People's Republic of China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Space Applied Physics and Chemistry, Ministry of Education, Department of Applied Chemistry, School of Science, Northwestern Polytechnical University, Xi'an 710072, People's Republic of China.
authors.forename: Yimeng
authors.initials: Y
authors.lastname: Qian
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Material, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Photochemical Conversion and Optoelectronic Material, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
authors.forename: Xuesong
authors.initials: X
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D002945:Cisplatin / Q000737:chemistry / Q000494:pharmacology; D054856:G-Quadruplexes; D006801:Humans; D020014:K562 Cells; D062105:Molecular Docking Simulation; D009944:Organoplatinum Compounds / Q000737:chemistry / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000378:metabolism*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*
chemical_list: C489427:MYC protein, human; D009944:Organoplatinum Compounds; D016271:Proto-Oncogene Proteins c-myc; D011725:Pyridines; D002945:Cisplatin
keywords: Alkynylplatinum(II) terpyridine; Anticancer drug design; Antiproliferative effect; G-quadruplex ligand; Molecular crowding