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Coordination‐Driven Self‐Assembly and Anticancer Potency Studies of Ruthenium–Cobalt‐Based Heterometallic Rectangles
Author(s) -
Singh Nem,
Jang Sunphil,
Jo JaeHo,
Kim Dong Hwan,
Park Dae Won,
Kim InHye,
Kim Hyunuk,
Kang Se Chan,
Chi KiWhan
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201603521
Subject(s) - ruthenium , autophagy , apoptosis , chemistry , pyridine , cancer cell , cytotoxicity , programmed cell death , stereochemistry , bimetallic strip , microbiology and biotechnology , cancer , medicinal chemistry , biochemistry , biology , in vitro , catalysis , genetics
Abstract Three new cobalt–ruthenium heterometallic molecular rectangles, 1 – 3 , were synthesized through the coordination‐driven self‐assembly of a new cobalt sandwich donor, (η 5 ‐Cp)Co[C 4 ‐ trans‐ Ph 2 (4‐Py) 2 ] (L ; Cp: cyclopentyl; Py: pyridine), and one of three dinuclear precursors, [( p ‐cymene) 2 Ru 2 (OO∩OO) 2 Cl 2 ] [OO∩OO: oxalato ( A 1 ), 5,8‐dioxido‐1,4‐naphthoquinone ( A 2 ), or 6,11‐dioxido‐5,12‐naphthacenedione ( A 3 )]. All of the self‐assembled architectures were isolated in very good yield (92–94 %) and were fully characterized by spectroscopic analysis; the molecular structures of 2 and 3 were determined by single‐crystal X‐ray diffraction analysis. The anticancer activities of bimetallic rectangles 1 – 3 were evaluated with a 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide (MTT) assay, an autophagy assay, and Western blotting. Rectangles 1 – 3 showed higher cytotoxicity than doxorubicin in AGS human gastric carcinoma cells. In addition, the autophagic activities and apoptotic cell death ratios were increased in AGS cells by treatment with 1 – 3 ; the rectangles induced autophagosome formation by promoting LC3‐I to LC3‐II conversion and apoptotic cell death by increasing caspase‐3/7 activity. Our results suggest that rectangles 1 – 3 induce gastric cancer cell death by modulating autophagy and apoptosis and that they have potential use as agents for the treatment of human gastric cancer.