Issue 48, 2009
From the journal:

Dalton Transactions

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

Jonathan F. Arambula,a   Jonathan L. Sessler,*a   Mark E. Fountain,a   Wen-hao Wei,a   Darren Magda*b  and  Zahid H. Siddik*c  

* Corresponding authors

a Department of Chemistry and Biochemistry, Texas Institute for Diagnostics and Drug Development, 1 University Station-A5300, The University of Texas, Austin, TX

b Pharmacyclics, Inc., 995 E. Arques Ave., Sunnyvale, CA, 94085

c Department of Experimental Therapeutics, UT M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 353, Houston, TX

Abstract

The synthesis of a new PEG-solubilized gadolinium texaphyrin (Gd-Tex) conjugate containing a malonate-Pt(NH3)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 an aquated Pt(NH3)2 species 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.

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

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Article information

DOI
https://doi.org/10.1039/B912089K
Article type
Paper
Submitted
19 Jun 2009
Accepted
15 Sep 2009
First published
07 Oct 2009

Dalton Trans., 2009, 10834-10840

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

J. F. Arambula, J. L. Sessler, M. E. Fountain, W. Wei, D. Magda and Z. H. Siddik, Dalton Trans., 2009, 10834 DOI: 10.1039/B912089K

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