title: Naphthalimides exhibit in vitro antiproliferative and antiangiogenic activities by inhibiting both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs).
abstract: Novel naphthalimide derivatives were designed and synthesized to modulate both topoisomerase II (topo II) and receptor tyrosine kinases (RTKs). Most target compounds exhibited effective and selective antiproliferative activities against three cancer cell lines by inhibiting topo II. The IC50 values ranged from 1.5 to 19.1 μM. Moreover, compounds 8d and 12d moderately inhibited various angiogenesis-related RTKs, including FGFR1, VEGFR2 and PDGFRα. The representative compound 8d was then proved to possess antiangiogenic activity, which was evidenced by the inhibition of migration and tube formation activities of HMEC-1 cells. To our knowledge, it is the first time naphthalimides were identified as tyrosine kinases inhibitors (TKIs) besides their conventional cytotoxicity.
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: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Chen
authors.forename: Linjiang
authors.initials: L
authors.lastname: Tong
authors.forename: Shaoying
authors.initials: S
authors.lastname: Tan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Ting
authors.initials: T
authors.lastname: Peng
authors.forename: Kun
authors.initials: K
authors.lastname: Han
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Hua
authors.initials: H
authors.lastname: Xie
authors.forename: Yufang
authors.initials: Y
authors.lastname: Xu
mesh_terms: D020533:Angiogenesis Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D006801:Humans; D015394:Molecular Structure; D053644:Naphthalimides / 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* / Q000378:metabolism; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D053644:Naphthalimides; D047428:Protein Kinase Inhibitors; D059005:Topoisomerase II Inhibitors; D020794:Receptor Protein-Tyrosine Kinases; D004250:DNA Topoisomerases, Type II
keywords: Angiogenesis; EGFR; FGFR; HMEC-1; Human Microvascular Endothelial Cells; Multitarget; Naphthalimide; PDGFR; RTK; Receptor Tyrosine Kinase; TKIs; Topo II; Topoisomerase II; Tyrosine kinase; VEGFR; epidermal growth factor receptor; fibroblast growth factor receptor; kDNA; kinetoplast DNA; platelet-derived growth factor receptor; topoisomerase II; tyrosine kinases inhibitors; vascular endothelial growth factor receptor