%0 Journal Article
%T In Vitro Cytotoxicity and In Vivo Antitumor Efficacy of Tetrazolato-Bridged Dinuclear Platinum(II) Complexes with a Bulky Substituent at Tetrazole C5
%J Inorganics | An Open Access Journal from MDPI
%D 2019
%R https://doi.org/10.3390/inorganics7010005
%X Tetrazolato-bridged dinuclear platinum(II) complexes ([{ cis-Pt(NH 3) 2} 2(¦Ì-OH)(¦Ì-5-R-tetrazolato- N2, N3)] 2+; tetrazolato-bridged complexes) are a promising source of next-generation platinum-based drugs. ¦Â-Cyclodextrin (¦Â-CD) forms inclusion complexes with bulky organic compounds or substituents, changing their polarity and molecular dimensions. Here, we determined by 1H-NMR spectroscopy, the stability constants for inclusion complexes formed between ¦Â-CD and tetrazolato-bridged complexes with a bulky, lipophilic substituent at tetrazole C5 (complexes 1¨C 3, phenyl, n-nonyl, and adamantyl substitution, respectively). We then determined the in vitro cytotoxicity and in vivo antitumor efficacy of complexes 1¨C 3 against the Colon-26 colorectal cancer cell line in the absence or presence of equimolar ¦Â-CD. Compared with the platinum-based anticancer drug oxaliplatin (1 R,2 R-diaminocyclohexane)oxalatoplatinum(II)), complex 2 had similar cytotoxicity, complex 3 was moderately cytotoxic, and complex 1 was the least cytotoxic. The cytotoxicity of the complexes decreased in the presence of ¦Â-CD. When we examined the in vivo antitumor efficacy of complexes 1¨C 3 (10 mg/kg) against homografted Colon-26 colorectal tumors in male BALB/c mice, they showed a relatively low tumor growth inhibition compared with oxaliplatin. However, in the presence of ¦Â-CD, complex 3 had higher in vivo antitumor efficacy than oxaliplatin, suggesting a new direction for future research into tetrazolato-bridged complexes with high in vivo antitumor activity. View Full-Tex
%U https://www.mdpi.com/2304-6740/7/1/5