Gadolinium texaphyrin (Gd-Tex)-malonato-platinum conjugates: Synthesis and comparison with carboplatin in normal and Pt-resistant cell lines

Abstract

The synthesis of a new PEG 3 -solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH 3 ) 2 moiety is described. The effect of the tumor localizing Gd-Tex macrocycle on platinum activity was evaluated in cell culture. The malonate moiety, analogous to that present in carboplatin, is expected to release Pt(NH 3 ) 2 under physiological conditions. The half-life in phosphate-buffered saline was found to be ca. 3 days at room temperature, and the hydrolytic product released from the conjugate was collected and confirmed as Pt-based by flameless atomic absorption spectrophotometry. Anti-proliferative activity was tested using A549 human lung cancer and A2780 human ovarian cancer cell lines. In both cell lines, the activity of the Gd-Tex conjugate was found to be similar to that of carboplatin. Efficacy against a Pt-resistant ovarian cell line greater than that displayed by carboplatin was also observed.

Bismuth– and lead–texaphyrin complexes: towards potential α-core emitters for radiotherapy

“…To determine the inherent cytotoxicity of 1a and 1b towards potential tumor targets, cell proliferation assays were conducted using an A2780 ovarian cancer cell line, which was recently found to display sensitivity towards MGd. 26 As shown in Fig. 5, both MBi and MPb gave IC 50 values of 2.2 and 2.9 μM, respectively.…”

A texaphyrin–oxaliplatin conjugate that overcomes both pharmacologic and molecular mechanisms of cisplatin resistance in cancer cells

“…1) that produced equivalent levels of intracellular Pt and DNA–Pt adducts in both sensitive A2780 and isogenic multifactorial-resistant 2780CP cells upon exposure to conjugate 2 . 18,19 This conjugate was designed to form qualitatively identical adducts to those induced by cisplatin or carboplatin. 18 Consequently, it displayed potent cytotoxicity in the A2780 human ovarian tumor model.…”

Texaphyrins: Tumor Localizing Redox Active Expanded Porphyrins

“…On this basis, it was concluded that the Pb(II) texaphyrin 15 and the Bi(III) texaphyrin 16 gave IC 50 values of 2.9 and 2.2 µM, respectively. This represents a 2–3 fold increase in cytotoxicity relative to MGd (6.3 µM) [116]. Based on these findings and considering the tumor selectivity properties of texaphyrins, we suggest that the texaphyrins could emerge as useful complexants for 212 Bi, 213 Bi, or 212 Pb and, as such, warrant further study as candidates for radiotherapy.…”

“…8). An ovarian cancer model, consisting of a platinum sensitive A2780 cell line and its isogenic platinum resistant 2780CP cell line, was chosen to determine whether this conjugate was effective in overcoming resistance [116]. …”