Redox-Activated Drug Delivery Properties and Cytotoxicity of Cobalt Complexes Based on a Fluorescent Coumarin-β-Keto Ester Hybrid

The search for new Co-III-based drug delivery systems has attracted considerable attention in recent years. In this work, two cobalt complexes with general formula [Co(L)Am](ClO4)(n) were synthesized, in which L- = (ethyl-3-(7-(diethylamino)-2-oxo-2H-chromen-3-yl)-3-oxopropanoate), a coumarin-beta-keto ester ligand, and Am is the auxiliary amine TPA (tris-(2-pyridylmethyl)amine) or Py(2)en (2-pyridylmethyl)-1,2-diamine). Complexation reactions yielded [Co-II(L)TPA]ClO4 (1) and [Co-III(L)Py(2)en](ClO4)(2) (2), and the Co-III complex (2) was investigated as a potential hypoxia-activated prodrug prototype. The redox potential of the Co-III/Co-II couple (+ 0.152 V vs. standard hydrogen electrode - SHE) was outside the suggested range for activation by cellular reductases. However, (2) was successfully able to release L- in the presence of sodium ascorbate, which was found to be slightly dependent on the O-2 concentration. In terms of cytotoxicity, (2) and HL were the least toxic compounds against the tumor cells tested (IC50 > 40 and 100 mu m) and nontoxic against normal cells. The results show that complex (2) is a reductively activated non-toxic carrier system.