Anticancer Activity and Autophagy Involvement of Self-Assembled Arene鈥揜uthenium Metallacycles

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• 作者：Abhishek Dubey ; Yong Joon Jeong ; Jae Ho Jo ; Sangkook Woo ; Dong Hwan Kim ; Hyunuk Kim ; Se Chan Kang ; Peter J. Stang ; Ki-Whan Chi
• 刊名：Organometallics
• 出版年：2015
• 出版时间：September 28, 2015
• 年：2015
• 卷：34
• 期：18
• 页码：4507-4514
• 全文大小：458K
• ISSN：1520-6041

文摘

A suite of six metallacycles (1鈥?b>6) was generated via coordination-driven self-assembly using the three dicarboxylate-bridged arene鈥揜u precursors [Ru₂(渭-畏⁴-OO鈭㎡O)(畏⁶-p-iPrC₆H₄Me)₂][CF₃SO₃]₂; (OO鈭㎡O = oxalate (A1), 2,5-dihydroxy-1,4-benzoquinonato (dobq) (A2), 5,8-dihydroxy-1,4-naphthoquinonato (donq) (A3); CF₃SO₃ = triflate) with one of two dipyridyl ligands (L1 and L2). The metallacycles were isolated in excellent yield (86鈥?2%) as triflate salts and characterized by proton (¹H) and carbon-13 (¹³C) nuclear magnetic resonance (NMR) and electrospray ionization鈥搈ass spectrometry (ESI-MS) to confirm their structural assignments. Single-crystal X-ray crystal analysis of 1 revealed that two L1 ligands bridged two A1 acceptors to form a rectangular architecture. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to evaluate the in vitro cytotoxicities relative to two chemotherapeutic agents: namely, cisplatin and doxorubicin. Metallacycles 3 and 6 potently inhibited the growth of HCT-15 human colon and AGS human gastric cancer cells. The hollow fiber (HF) assay was performed to investigate the in vivo antitumor activities of metallacycles 3 and 6. Metallacycle 6 was more effective in inhibiting HCT-15 cells than metallacycle 3 in both in vitro and in vivo studies. Moreover, 3 and 6 induced autophagic activity in HCT-15 cells. These results suggested that the autophagic response elicited by metallacycles 3 and 6 could mediate the anticancer effects observed in human colorectal cancer cells.