Photoinduced reduction of Pt^IV within an anti-proliferative Pt^IV-texaphyrin conjugate

In an effort to increase the stability and control the platinum reactivity of platinum-texaphyrin conjugates, two Pt^IV 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 Pt^II 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 Pt ^IV center within this conjugate undergoes photoinduced reduction to Pt^II upon exposure to glass-filtered daylight, resulting in an entity that binds DNA in a controlled manner. Under conditions in which the Pt ^IV complex is reduced to the corresponding Pt^II species, these new conjugates demonstrated potent anti-proliferative activity in both test ovarian cancer cell lines. Platinum(IV) prodrug: Two new platinum(IV)-texaphyrin conjugates were designed and synthesized in order to target preferentially cancer cells and to deliver platinum(II). Protected from light, these two compounds are stable in aqueous environments. However, upon reduction or upon exposure to visible light, an active Pt^II species is released and binds to DNA. Potent anti-proliferative activity in test ovarian cancer cell lines was also seen for the Pt^IV-texaphyrin conjugates of this study.