Abstract
Diabetes mellitus is closely related to diseases such as macrovascular disorders. The main causes of macrovascular disorders are the products of non-enzymatic glycation reactions, i.e., advanced glycation end products (AGEs). Zinc (Zn) complexes are known to exhibit hypoglycemic activity, with some Zn complexes suppressing AGE formation. In this study, we show that the relationship between the suppressive activities against AGE formation in Zn complexes and hypoglycemic activity depends on the coordination mode. We compare the Zn(O4)-type zinc complexes [Zn(mal)2] and [Zn(opd)2] and the Zn(S2O2)-type Zn complexes [Zn(tmal)2] and [Zn(opt)2]. The formation of fluorescent AGEs is suppressed by all Zn complexes, while pentosidine formation is suppressed by [Zn(mal)2] (IC50 = 308 ± 88 μM) and [Zn(opd)2] (IC50 = 47 ± 7 μM) but not by [Zn(tmal)2] or [Zn(opt)2]. The Zn(S2O2)-type Zn complexes are therefore predicted to exhibit stronger antiglycation effects than Zn(O4)-type Zn complexes: however, Zn(S2O2)-type Zn complexes do not always exhibit strongly suppress antiglycation or pentosidine formation. We found that Zn(O4)-type Zn complexes exhibit a stronger antiglycation effect than Zn(S2O2)-type Zn complexes.
