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

Abstract

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](ClO 4 ) n were synthesized, in which L – = (ethyl‐3‐(7‐(diethylamino)‐2‐oxo‐2H‐chromen‐3‐yl)‐3‐oxopropanoate), a coumarin‐β‐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]ClO 4 (1) and [Co III ( L )Py 2 en](ClO 4 ) 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 (IC 50 > 40 and 100 µ m ) and nontoxic against normal cells. The results show that complex (2) is a reductively activated non‐toxic carrier system.