Photoinduced Reduction of PtIV within an Anti‐Proliferative PtIV–Texaphyrin Conjugate |
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Authors: | Dr. Grégory Thiabaud Dr. Jonathan F. Arambula Prof. Zahid H. Siddik Prof. Jonathan L. Sessler |
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Affiliation: | 1. Department of Chemistry and Institute for Cellular and Molecular Biology, The University of Texas at Austin, 105 E. 24th Street‐ Stop A5300, Austin, Texas 78712‐1224 (USA);2. The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Unit Number: 1950, Houston, TX 77030 (USA) |
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Abstract: | In an effort to increase the stability and control the platinum reactivity of platinum–texaphyrin conjugates, two PtIV conjugates were designed, synthesized, and studied for their ability to form DNA adducts. They were also tested for their anti‐proliferative effects using wild‐type and platinum‐resistant human ovarian cancer cell lines (A2780 and 2780CP, respectively). In comparison to an analogous first‐generation PtII chimera, one of the new conjugates provided increased stability in aqueous environments. Using a combination of 1H NMR spectroscopy and FAAS (flameless atomic‐absorption spectrometry), it was found that the PtIV center within this conjugate undergoes photoinduced reduction to PtII upon exposure to glass‐filtered daylight, resulting in an entity that binds DNA in a controlled manner. Under conditions in which the PtIV complex is reduced to the corresponding PtII species, these new conjugates demonstrated potent anti‐proliferative activity in both test ovarian cancer cell lines. |
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Keywords: | conjugates drug design photo‐activation platinum texaphyrin |
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