Labeling dansyl molecular probe in aldazines to decipher conformational selected inhibition pathway from early to advanced glycation

Prolonged hyperglycemia exacerbates diabetes through the formation of early Amadori-glycoxidation, intermediate reactive dicarbonyl species and advanced cross-linked aggregates. The study utilizes multi-spectroscopies based biophysical analyses to encompass an early to advanced stage inhibition of fructose (Fru) and methylglyoxal mediated bovine serum albumin (BSA) glycation (Fru-gBSA and methylglyoxal-gBSA) by introducing dansyl labelled molecular probe in the privileged scaffold pseudo C2‒symmetric transoid aldazines (bis-aldimine) framework. The study thus explores the pharmacophoric role of aldazine moiety through the conformational-binding selection of s-trans dansylated-bis-vanillin aldimines (DVBA-1) to investigate the inhibition mechanism of BSA glycation from early Amadori-glycoxidation to advanced cross-linking. Conformational studies in association with molecular docking and dynamic simulation reflects a distinctive binding between IIA and IIIA sub-domain of BSA of a specific rotameric transoid conformation of DVBA-1, among all transoid conformers, which causes secondary structural perturbation and glycation micro-environment alteration. This strategy supports the primary interactions of aldazine pharmacophore of DVBA-1 near sugar-binding domain of BSA resulting inhibition of glycation.