New Potential Anticancer Agent of Carborane Derivatives: Selective Cellular Interaction and Activity of Ferrocene-Substituted Dithio-o-carborane Conjugates

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• 作者：Chunhui Wu ; Hongde Ye ; Wenjuan Bai ; Qingning Li ; Dadong Guo ; Gang Lv ; Hong Yan ; Xuemei Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2011
• 出版时间：January 19, 2011
• 年：2011
• 卷：22
• 期：1
• 页码：16-25
• 全文大小：550K
• 年卷期：v.22,no.1(January 19, 2011)
• ISSN：1520-4812

文摘

The large diversity of structures and unique bonding modes of organometallic complexes make them possible to act as promising candidate therapeutic agents. In this study, the new type of ferrocene-substituted dithio-o-carborane conjugates (FcSB1, FcSB2, and FcSBCO) has been synthesized, and their in vitro antineoplastic activities have been explored by means of the electrochemical study, the real time cell electronic sensing (RT-CES) system, and biological assays. The conjugate鈭抍ell interactions were first monitored by electrochemistry, and the results show different cell uptake efficiency for FcSB1, FcSB2, and FcSBCO toward target cells. Both the highly hydrophobic ferrocenyl and carboranyl groups render the conjugates able to rapidly enter cells and exert acute cytotoxicity after 4 h incubation in serum-free media. However, FcSB1, FcSB2, and FcSBCO display different inhibition efficiencies toward SMMC-7721 and HepG2 cancer cells via the G₀/G₁ arrest mechanism in a physiological environment. The anticancer activity is in the order FcSB2 > FcSB1 > FcSBCO, which is parallel to the order of the redox potentials of the ferrocenyl groups in the three complexes. In particular, FcSB1 and FcSB2 display a potent selective inhibition effect on the proliferation of the cancer cell lines SMMC-7721 and HepG2, but almost no effect on the normal cell line, the human embryonic lung fibroblast (HELF) cells. Thus, these results may provide some clues for use of the ferrocene鈭抍arborane conjugates in developing anticancer drugs.