title: Synthesis and the interaction of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines with telomeric DNA as lung cancer inhibitors.
abstract: A novel series of 2-(1H-pyrazol-4-yl)-1H-imidazo[4,5-f][1,10]phenanthrolines were designed, synthesized and evaluated for their antitumor activity against lung adenocarcinoma by CCK-8 assay, electrophoretic mobility shift assay (EMSA), UV-melting study, wound healing assay and docking study. These compounds showed good inhibitory activities against lung adenocarcinoma. Especially compound 12c exhibited potential antiproliferative activity against A549 cell line with the half maximal inhibitory concentration (IC50) value of 1.48 μM, which was a more potent inhibitor than cisplatin (IC50= 12.08 μM) and leading compound 2 (IC50= 1.69 μM), and the maximum cell inhibitory rate being up to 98.40%. Moreover, further experiments demonstrated that compounds 12a-d can strongly interact with telomeric DNA to stabilize G-quadruplex DNA with increased ΔTm values from 12.44 to 20.54 °C at a ratio of DNA to compound 1:10. These results implied that growth inhibition of A549 cells mediated by these phenanthroline derivatives is possibly positively correlated to the fact their interaction with telomeric G-quadruplexs.
authors.affiliation: Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Jiachun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.
authors.forename: Sijia
authors.initials: S
authors.lastname: Wang
authors.affiliation: Lab of Molecular Immunology, Virus Inspection Department, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, 310051, China. Electronic address: ylwu@cdc.zj.cn.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Lab of Chemical Biology and Molecular Drug Design, College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China. Electronic address: wzhang63@zjut.edu.cn.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000072283:A549 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D054856:G-Quadruplexes / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D010618:Phenanthrolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016615:Telomere / Q000187:drug effects / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D010618:Phenanthrolines; D011720:Pyrazoles
keywords: Antiproliferative activity; Lung adenocarcinoma; Phenanthroline; Telomeric G-quadruplex