Determination of the Effects of Copper Coordination Compounds withThiosemicarbazones on the in vitro Formation of Advanced Glycation EndProducts of the Pentosidine-like and Vesperlysine-like Types

Introduction: Thiosemicarbazones are heterocyclic compounds with diverse biological properties. They can exhibit anticancer, antioxidant, and pro-oxidative properties depending on their structure. The Advanced Glycation End-Products (AGE) pentosidine-like and vesperlysinelike compounds are actually involved in oxidative stress and diseases. This study aimed to determine the effect of copper-thiosemicarbazone coordination compounds for inhibiting AGEs with a comparison to a known pro-oxidative compound, Doxorubicin. Methods: Several copper coordination compounds of thiosemicarbazones were tested at two different concentrations (10.0 μmol/L and 1.0 μmol/L). The levels of pentosidine-like and vesperlysine- like AGEs were estimated and compared to those of controls and values after treatment with doxorubicin. Results: A high concentration of doxorubicin, CMD-8, MG-22, and TIA-160 remarkably enhanced the level of pentosidine-like AGE. Their values were up to four times higher than the control. For vesperlysine-like AGE, the effect was variable: the concentrations of CMD-8 and MG-22 remarkably increased the level, whereas CMC-34 remarkably decreased it. In the 1.0 μmol/L concentration, the modulating effect on AGE was less prominent; some compounds still affected the level. Discussion: The differing reactions of AGE subclasses imply distinct molecular mechanisms controlling pentosidine-like and vesperlysine-like AGE formation. The decrease levels of various AGE subclasses imply potential antiglycation/protective effects of certain compounds. Conclusion: Concentration- and structure-dependent effects of copper-thiosemicarbazones on AGE accumulation occur. There is a need in separate assessment of AGE subclasses to accomplish the evaluation of the metabolic role and therapeutic potential.