Metal鈥揂rene Complexes with Indolo[3,2-c]-quinolines: Effects of Ruthenium vs Osmium and Modifications of the Lactam Unit on Intermolecular Interactions, Anticancer Activity, Cell Cycle, and Cel

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• 作者：Lukas K. Filak ; Simone G枚schl ; Petra Heffeter ; Katia Ghannadzadeh Samper ; Alexander E. Egger ; Michael A. Jakupec ; Bernhard K. Keppler ; Walter Berger ; Vladimir B. Arion
• 刊名：Organometallics
• 出版年：2013
• 出版时间：February 11, 2013
• 年：2013
• 卷：32
• 期：3
• 页码：903-914
• 全文大小：581K
• 年卷期：v.32,no.3(February 11, 2013)
• ISSN：1520-6041

文摘

Six novel ruthenium(II)鈥?and osmium(II)鈥揳rene complexes with three modified indolo[3,2-c]quinolines have been synthesized in situ starting from 2-aminoindoloquinolines and 2-pyridinecarboxaldehyde in the presence of [M(p-cymene)Cl₂]₂ (M = Ru, Os) in ethanol. All complexes have been characterized by elemental analysis, spectroscopic techniques (¹H, ¹³C NMR, IR, UV鈥搗is), and ESI mass spectrometry, while four complexes were investigated by X-ray diffraction. The complexes have been tested for antiproliferative activity in vitro in A549 (non-small cell lung), SW480 (colon), and CH1 (ovarian) human cancer cell lines and showed IC₅₀ values between 1.3 and >80 渭M. The effects of Ru vs Os and modifications of the lactam unit on intermolecular interactions, antiproliferative activity, and cell cycle are reported. One ruthenium complex and its osmium analogue have been studied for anticancer activity in vivo applied both intraperitoneally and orally against the murine colon carcinoma model CT-26. Interestingly, the osmium(II) complex displayed significant growth-inhibitory activity in contrast to its ruthenium counterpart, providing stimuli for further investigation of this class of compounds as potential antitumor drugs.