Abstract: “The FDA approved anticancer drug arsenic trioxide (As2O3) is highly efficient for treatment of acute promyelocytic leukemia, but due to its rapid renal clearance in the form of arsenous acid, As(OH)3, it has been ineffective in the treatment of solid cancers. A new class of potent anticancer agents that contain As(OH)2 moiety bound to platinum(II) center, arsenoplatins [Pt(µ-NHC(R)O)2XAs(OH)2] (R=CH3 or CH3CH2), X=Cl-, SCN-), have been synthesized. A high Pearson correlation coefficient (r = 0.96) was obtained while comparing anticancer activity of Arsenoplatin-2 (R = CH3CH2, X=Cl- ; AP-2) to As2O3 in the NCI-60 screen, suggesting the two compounds act in a similar manner. This project aims to synthesize, characterize, and test the anticancer activity of an iodide analog of AP-2, labeled AP-4. X-ray, NMR, and elemental analysis have been completed to determine the structure and purity of this new compound. The cytotoxicity of AP-4 in the triple negative breast MDA-MB-231 cancer cell line has been evaluated by MTS cell proliferation assay. Interaction of AP-4 with the biologically important molecule glutathione (GSH) was assessed by fluorescent detection assay. GSH depletion has been shown to sensitize cancer cells that are resistant to platinum drugs. The effect of AP-4 concentrations on the GSH level is discussed. Based on current results, AP-2 and AP-4 may act as a delivery vehicle for As2O3, overcoming one of the primary limitations of As2O3 as a drug for solid cancers.”
East Central IL ACS Undergraduate Research Conference
Thank you for joining us for the 5th Annual ECI-ACS conference!
What is the mechanism or mechanisms of Pt resistance in these cancer cells? How does changing the Cl to I help prevent resistance?
Can you comment on why the Pt-As bond is weaker when the Cl is substituted for the I? Also do you see a change in the As-O bond lengths as well?
One other question – do you think a dimeric As compound work as well, instead of a Pt-As compound? Why or why not?
Nice amount of work / presentation.
Can you comment/explain the difference(s) you would expect or were measuring in your NMR spectrum between AP-2 and AP-4. I believe you stated that you used NMR to determine product formation and/or purity. What effect does the substitution of iodide for chloride have in the proton NMR spectrum?