A new platinum-complex showing easy preparation, promising anti-tumor activity, and better efficacy and distribution properties than oxaliplatin.
Current clinically used chemotherapeutic platinum drugs can trigger severe toxic effects. To develop a model system for the evaluation of the therapeutic efficacy and the toxic effects of new platinum agents, we have synthesized a new compound N-[(2S,3R,4R,5R)-2,3,4,5,6-pentahydroxylhex-1-yl]-L-hydroxyproline dichloroplatinum(ii) (PHDP), compared its in vitro anti-proliferation activity, in vivo anti-tumor activity and safety to those of oxaliplatin, and correlated all these biological actions with the platinum occurring in the spleen, kidney, heart, brain, blood, tumor tissue, urine and faeces of the treated mice. We explored the atomic absorption based determinations of the platinum which occurred in the spleen, kidney, heart, brain, blood, tumor tissue, urine and faeces and constitute a model system that can be generally used in the investigation of the novel platinum agents.
College of Pharmaceutical Sciences, Capital Medical University, Beijing 100069, PR China.
Yuji
Y
Wang
Guifeng
G
Kang
Ming
M
Zhao
Jianhui
J
Wu
Xiaoyi
X
Zhang
Yifan
Y
Yang
Jiawang
J
Liu
Shiqi
S
Peng
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D009929:Organ Size; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D000077150:Oxaliplatin; D014018:Tissue Distribution
D000970:Antineoplastic Agents; C572205:N-((2S,3R,4R,5R)-2,3,4,5,6-pentahydroxylhex-1-yl)-L-hydroxyproline dichloroplatinum(II); D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D006909:Hydroxyproline