Introduction of Fluorine into Antitumor-Active Dinuclear Platinum(II) Complexes Leads to Modulation of In Vivo Antitumor Activity in Mice.
Inorg Chem
; 61(31): 12155-12164, 2022 Aug 08.
Article
em En
| MEDLINE
| ID: mdl-35876345
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Platina
/
Antineoplásicos
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article