title: Novel metal complexes of naphthalimide-cyclam conjugates as potential multi-target receptor tyrosine kinase (RTK) inhibitors: synthesis and biological evaluation.
abstract: A novel series of metal complexes of naphthalimide-cyclam conjugates were synthesized and their in vitro antitumor activities were evaluated. The newly-synthesized compounds showed huge diversity of antiproliferative potency due to variety of metal ions and length of alkyl chains, among which the Zn(II) and Cr(III) complexes exhibited comparable antiproliferative activities with amonafide via multiple tyrosine kinase inhibition. Further research revealed that the representative compound 8a displayed broad-spectrum antiproliferative activity against 15 cancer cell lines with average IC50 value 10.18 ± 3.25 μM, and effective antiangiogenic activity on human microvascular endothelial cells (HMEC-1). In brief, metal complexes of naphthalimide-cyclam conjugates were firstly designed and synthesized as multi-target tyrosine kinase inhibitors and proved of their antitumor capacities.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Shaoying
authors.initials: S
authors.lastname: Tan
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Han
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Linjiang
authors.initials: L
authors.lastname: Tong
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yiqi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: chenzhuo@ecust.edu.cn.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: hxie@simm.ac.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.affiliation: Division of Anti-tumor Pharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Xuhong
authors.initials: X
authors.lastname: Qian
authors.affiliation: State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of Chemical Biology, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: yfxu@ecust.edu.cn.
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015536:Down-Regulation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006571:Heterocyclic Compounds / Q000737:chemistry*; D006801:Humans; D053644:Naphthalimides / Q000737:chemistry*; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D053644:Naphthalimides; D009942:Organometallic Compounds; D047428:Protein Kinase Inhibitors; C024560:cyclam; D020794:Receptor Protein-Tyrosine Kinases
keywords: Antiangiogenesis; Antiproliferation; Cyclam; Metal complexes; Naphthalimide; RTK inhibitors