Tumor inhibition by metallocenes: Antitumor activity of titanocene dihalides (C5H5)2TiX2 (X=F, Cl, Br, I, NCS) and their application in buffered solutions as a method for suppressing drug-induced side effects

Abstract

The antitumor activity of titanocene dihalides (C5H5)2TiX2 with X=F, Cl, Br, I, NCS is investigated against Ehrlich ascites tumor in CF 1 mice. Varying doses of the compounds are applied as single i.p. injections 24 h p.t.t. both in non-buffered (pH 1.4-3.9) and buffered (pH 4.2-5.9) solutions or suspensions, all of the substances achieving in optimum doses cure rates of 100% on day 120 p.t.t. This corresponds to I.L.S. values of 600-750% referred to the untreated controls. Some drug-induced side effects, especially the appearance of postperitonitic symptoms several weeks after i.p. application of higher doses of titanocene dihalides, are strikingly reduced by pH elevation in the injected drug solutions.

Cytotoxic Titanium Salan Complexes: Surprising Interaction of Salan and Alkoxy Ligands

“…It showed an IC 50 of (1.2 AE 0.4) mm in HeLa S3 and (3.0 AE 1.3) mm in Hep G2 cells. All IC 50 values are given as mean values from at least three independent experiments each done in four replicates.…”

Designing organometallic compounds for catalysis and therapy

“…157 These involve the encapsulation of a relatively hydrophobic complex (e.g. Pd(acac) 2 ) within a hydrophobic pocket of a metal-containing host (69). These metalla-cages ( Figure 27) can release hydrophobic drugs like pyrene-R (70) efficiently following uptake into a cell.…”

A Cobaltocenium–Peptide Bioconjugate Shows Enhanced Cellular Uptake and Directed Nuclear Delivery

“…[5,6] Further examples include {Ru(arene)} complexes, [7] several {Co(CO) 2 (alkyne)} derivatives [8][9][10][11] in addition to the well-studied titanocene dichloride which has been in clinical trials. [12][13][14][15] DNA interaction has been suggested as the mode of action, at least for some of the organometallic antitumor agents. However, the question of nuclear localization, although a prerequisite for this mode of action, has usually been taken for granted without ever being investigated in detail.…”