Coordination-Driven Self-Assembly and Anticancer Potency Studies of Ruthenium-Cobalt-Based Heterometallic Rectangles.
Three new cobalt-ruthenium heterometallic molecular rectangles, 1-3, were synthesized through the coordination-driven self-assembly of a new cobalt sandwich donor, (η5-Cp)Co[C4-trans-Ph2(4-Py)2] (L; Cp: cyclopentyl; Py: pyridine), and one of three dinuclear precursors, [(p-cymene)2Ru2(OO∩OO)2Cl2] [OO∩OO: oxalato (A1), 5,8-dioxido-1,4-naphthoquinone (A2), or 6,11-dioxido-5,12-naphthacenedione (A3)]. 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.
Department of Chemistry, University of Ulsan, Ulsan, 44610, Republic of Korea.
Nem
http://orcid.org/0000-0003-2952-3385
N
Singh
Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, Republic of Korea.
Sunphil
S
Jang
Department of Chemistry, University of Ulsan, Ulsan, 44610, Republic of Korea.
Jae-Ho
JH
Jo
Department of Chemistry, University of Ulsan, Ulsan, 44610, Republic of Korea.
Dong Hwan
DH
Kim
Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, Republic of Korea.
Dae Won
DW
Park
Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, Republic of Korea.
InHye
I
Kim
Energy Materials Laboratory, Korea Institute of Energy Research, Daejeon, 34129, Republic of Korea. hyunuk@kier.re.kr.
Hyunuk
H
Kim
Department of Oriental Biotechnology, College of Life Sciences, Kyung Hee University, Yongin, 17104, Republic of Korea. sckang@khu.ac.kr.
Se Chan
SC
Kang
Department of Chemistry, University of Ulsan, Ulsan, 44610, Republic of Korea. kwchi@ulsan.ac.kr.
Ki-Whan
KW
Chi
antitumor agents; cobalt; metallacycles; ruthenium; self-assembly