論文 - 詳細
| RRC ID | 72210 |
|---|---|
| 著者 | Uemura M, Hiramoto K, Yoneyama H, Harusawa S, Komeda S. |
| タイトル | Introduction of Fluorine into Antitumor-Active Dinuclear Platinum(II) Complexes Leads to Modulation of In Vivo Antitumor Activity in Mice. |
| ジャーナル | Inorg Chem |
| Abstract |
Tetrazolato-bridged dinuclear platinum(II) complexes ([{cis-Pt(NH3)2}2(μ-OH)(μ-5-R-tetrazolato-N2,N3)]2+; tetrazolato-bridged complexes) show remarkable cytotoxic effects in vitro and antitumor activity in vivo. Here, we examined the structure-activity relationship of a series of fluorine-containing derivatives (R = CFH2, CF2H, or CF3), focusing on their lipophilicity, cellular accumulation, cytotoxicity, interactions with a nucleobase and double-stranded deoxyribonucleic acid, and in vivo antitumor efficacy. Fluorination had a little effect on the properties of the derivatives in vitro; however, marked differences in in vitro cytotoxicity and in vivo tumor growth inhibition activity were observed. In BALB/c mice bearing colon-26 tumors, the antitumor efficacies of the derivatives were markedly altered, even by changing the number of fluorine atoms by one. In addition, one derivative, [{cis-Pt(NH3)2}2(μ-OH)(μ-5-difluoromethyltetrazolato-N2,N3)](NO3)2, showed a significantly higher antitumor efficacy compared with oxaliplatin, a current first-line drug and the only platinum-based drug approved for the treatment of colon cancer. Together, the present results indicate that introducing fluorine into tetrazolato-bridged complexes may be useful for modulating in vivo activities. |
| 巻・号 | 61(31) |
| ページ | 12155-12164 |
| 公開日 | 2022-8-8 |
| DOI | 10.1021/acs.inorgchem.2c01126 |
| PMID | 35876345 |
| MeSH | Animals Antineoplastic Agents* / pharmacology Cisplatin / pharmacology Fluorine Mice Organoplatinum Compounds / pharmacology Platinum* / pharmacology Tetrazoles / pharmacology |
| IF | 4.825 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 5 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | Colon-26(RCB2657) |