抄録
Objective: Glycative stress is induced by the modification of proteins by reactive aldehydes generated during glucose metabolism and lipid peroxidation. The present study aimed to clarify the structure–activity relationships underlying the anti-glycation activity of vitamin B6 compounds and to investigate a novel anti-glycation mechanism targeting reactive aldehydes.
Methods: Four vitamin B6 compounds (pyridoxine, 4-deoxypyridoxine, pyridoxal, and pyridoxamine), various pyridine derivatives, and corresponding benzene derivatives were evaluated. Anti-glycation activity was assessed using a human serum albumin (HSA)-glucose glycation model (60 °C, 40 h). The inhibitory effects on the formation of fluorescent advanced glycation end products (AGEs), pentosidine, 3-deoxyglucosone (3DG), glyoxal (GO), and methylglyoxal (MGO) were determined. DPPH radical scavenging activity was also measured to examine the relationship between antioxidant and anti-glycation activities.
Results: Among the vitamin B6 compounds, pyridoxal and pyridoxamine exhibited high anti-glycation activities, indicating that the functional group at the 4-position is an important determinant of anti-glycation activity. Among the pyridine derivatives, both the type and substitution position of the functional group influenced anti-glycation activity, with aldehyde- containing derivatives showing marked position-dependent differences in inhibitory activity. Pyridine derivatives generally exhibited higher anti-glycation activity than the corresponding benzene derivatives, highlighting the contribution of the pyridine ring. The inhibitory effects on reactive carbonyl intermediates varied among compounds and endpoints, with several compounds showing marked inhibition of GO, MGO, and/or 3DG formation. However, these activities did not clearly correlate with DPPH radical scavenging activity, indicating that the anti-glycation effects cannot be explained solely by antioxidant mechanisms.
Conclusion: The present study demonstrated that the anti-glycation activity of vitamin B6 compounds and related pyridine derivatives is influenced by three structural factors: the pyridine ring, the type of functional group, and its substitution position. Based on these findings, we propose the Pyridine ring–functional group cooperative model and provide evidence supporting the Aldehyde Trap concept, in which reactive aldehydes are selectively targeted and neutralized. These findings establish a conceptual framework linking structural chemistry with reactive aldehyde regulation and provide a basis for developing next-generation aldehyde-targeted anti-glycation strategies for the control of glycative, electrophilic, and metabolic stress.
