In-vitro anti-tumor activity studies of bridged and unbridged benzyl-substituted titanocenes.
The benzyl-substituted ansa-titanocenes [1,2-di(cyclopentadienyl)-1,2-di-(4-N,N-dimethylaminophenyl)ethanediyl] titanium dichloride (Titanocene X) and [1,2-di(cyclopentadienyl)-1,2-bis(m-dimethoxyphenyl)ethanediyl] titanium dichloride (Titanocene Z), and the benzyl-substituted unbridged titanocene bis-[(p-methoxybenzyl)cyclopentadienyl] titanium(IV) dichloride (Titanocene Y) were tested on the growth of a wide variety of tumor cells in vitro on a panel of 36 human tumor cell lines containing 14 different tumor types investigated in a cellular proliferation assay. Titanocene Y with a mean IC50 value of 65.8 x 10 mol/l over the full panel of 36 cancer cell lines reaches the activity of cisplatin with 14.7 x 10 mol/l within a factor of 4, whereas Titanocene X and Z show significantly less cytotoxic activity. Titanocene Y is most effective on pleura mesothelioma, and uterine and renal cell cancer, where the IC50 values are comparable or significantly better than for cisplatin. In particular, in the case of renal cell cancer and pleura mesothelioma there is an obvious lack of chemotherapeutic reagents, which might be filled by Titanocene Y, where a very promising cytotoxic effect in comparison with cisplatin could be shown.
Kelter
Gerhard
G
Oncotest GmbH, Institute of Experimental Oncology, Freiburg, Germany.
Sweeney
Nigel J
NJ
Strohfeldt
Katja
K
Fiebig
Heinz-Herbert
HH
Tacke
Matthias
M
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy*; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use*
C507877:(1,2-di(cyclopentadienyl)-1,2-di(3-dimethoxyphenyl)ethanediyl)titanium dichloride; C507876:(1,2-di(cyclopentadienyl)-1,2-di(4-N,N-dimethylaminophenyl)ethanediyl)titanium dichloride; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C507878:bis((4-methoxybenzyl)cyclopentadienyl)titanium(IV) dichloride