Antiglycation activity of nonvasodilatory beta blockers highlights acebutolol with reduced glycation markers and altered phosphoprotein expression

Advanced glycation end products (AGEs) contribute to diabetic vascular injury through oxidative and pro-inflammatory signaling, but the anti-glycation potential of non-vasodilatory β-blockers (NVBBs) is unclear. To evaluate the anti-glycation activity of selected NVBBs (alprenolol, nadolol, penbutolol, sotalol, acebutolol, and bisoprolol) using in vitro and in silico models. Protein glycation was assessed in bovine serum albumin (BSA) models using six glycating agents. Acebutolol, selected from the comparative BSA screen, was docked against 21 glycation- and signaling-associated protein structures and evaluated in hyperglycemic human umbilical vein endothelial cells (HUVECs) for glycation, oxidation, apoptosis-related, and PI3K/Akt/mTOR-associated phosphoprotein readouts. All NVBBs reduced multiple AGE subtypes in carbohydrate induced models. Acebutolol showed the broadest observed activity profile across the tested conditions, including reductions in argpyrimidine of 55.71%, pentosidine of 53.36%, and vesperlysine of 41.88%, and exceeded aminoguanidine for selected readouts. In HUVECs, 100 µg/mL acebutolol reduced selected glycation and oxidation-associated readouts, including total AGEs by 28.1%, advanced oxidation protein products by 40.5%, and NADPH oxidase activity by 23.2%. At 20–80 µg/mL, marked changes were observed in several measured phosphoproteins, including p-mTOR, p-S6RP, and p-BAD. Acebutolol showed a broad anti-glycation profile in the comparative BSA screen and altered selected glycation, oxidation, and signaling-associated readouts in hyperglycemic HUVECs. The molecular docking and cellular findings warrant confirmation in direct mechanistic studies.