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Updated: Jun 4, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
Overcoming biochemical pharmacologic mechanisms of platinum resistance with a texaphyrin-platinum conjugate
Jonathan F Arambula1, Jonathan L Sessler, Zahid H Siddik
1Department of Chemistry and Biochemistry, Texas Institute for Diagnostics and Drug Development, The University of Texas, Austin, TX 78712-0165, USA.
Abstract:
In our effort to investigate further texaphyrin conjugation as a means of increasing delivery and accumulation of known anticancer platinum agents in cancer cells, we have continued our studies on the mode of action of a texaphyrin-platinum conjugate, particularly in cisplatin-resistant tumor cells that are characterized by several mechanisms of resistance, including reduced drug accumulation. Our results provide support for the proposal that intracellular platinum and Pt-DNA adduct levels were significantly increased using our conjugate relative to corresponding Pt controls. Moreover, no differences were found in cellular accumulation and Pt-DNA adduct formation between Pt sensitive and Pt resistant ovarian cells. As a result, resistance to the conjugate was lower than cisplatin in resistant cells. Based on these results we conclude that texaphyrin conjugation provides a promising strategy for overcoming biochemical pharmacologic mechanisms of resistance.
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