title: 2'-chloro-4'-aminoflavone derivatives selectively targeting hepatocarcinoma cells: convenient synthetic process, G(2)/M cell cycle arrest and apoptosis triggers.
abstract: A series of 2'-chloro-4'-nitroflavone and 2'-chloro-4'-aminoflavone derivatives were synthesized by a convenient synthetic process. The in vitro anti-proliferation ability of these compounds was evaluated against hepatocarcinoma cells (HepG2), breast adenocarcinoma cells (MCF-7), and human chronic myelogenous leukemia cells (K562). Most of synthetic compounds possessed notable anti-proliferation activity against HepG2 cells and little activity against MCF-7 cells and K562 cells. In particular, compounds 4c and 4e exhibited high anti-proliferation activity against HepG2 cells with IC(50) at about 2.0 µM. Further toxicity screening toward normal human hepatocytes indicated that some compounds had low toxicity against normal liver cells, among which 4e displayed very weak effects on QSG7701 and HL7702 cells, with IC(50) values >100 and 50 µM, respectively. Compound 4c, with the best anti-proliferation activity in amino-substituted flavones (IC(50) = 2.0 µM), was selected for further evaluation of its effects on apoptosis and the cell cycle. HepG2 cells were exposed to this compound at 10 µM, which induced nuclear disassembly and DNA fragmentation. Flow cytometry analysis suggested that the population of apoptotic cells greatly increased in the 4c-treated HepG2 cells, and the cell cycle was arrested at the G(2)/M phase.
authors.affiliation: Department of Chemistry, Tsinghua University, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Jin
authors.forename: Nannan
authors.initials: N
authors.lastname: Zhang
authors.forename: Chunyan
authors.initials: C
authors.lastname: Tan
authors.forename: Dan
authors.initials: D
authors.lastname: Gao
authors.forename: Cunlong
authors.initials: C
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
authors.forename: Chunmei
authors.initials: C
authors.lastname: Gao
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.forename: Shangfu
authors.initials: S
authors.lastname: Li
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005434:Flow Cytometry; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D020014:K562 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; C413760:aminoflavone