Oxindole-based chalcones: synthesis and their activity against glycation of proteins

Abstract

Diabetes mellitus, a metabolic disorder, is characterized by a substantial hyperglycaemia. Prevalence of hyperglycaemia for longer period of time can cause nonenzymatic condensation of sugar in blood with amino group of protein and give rise to advanced glycation end products (AGEs). AGEs play a major role in the onset of late diabetic complications including diabetic retinopathy, nephropathy, neuropathy and cardiovascular diseases. There is a need to establish potential therapeutic regimens that can effectively inhibit the formation of AGEs. To this end a series of novel oxindole-based chalcones have been investigated for their antiglycation potential. Analogues 1 (IC50 = 155.22 ± 2.98 µM), 3 (IC50 = 195.95 ± 0.43 µM), 4 (IC50 = 289.47 ± 2.47 µM), 5 (IC50 = 222.44 ± 4.03 µM), 7 (IC50 = 251.27 ± 2.80 µM), and 20 (224.23 ± 1.93 µM) showed potent inhibitory activity against glycation compared to the reference Rutin (IC50 = 294.5 ± 1.5 µM). These results reveal that multiple hydroxyl substituents and their position on the aromatic ring play a key role in inhibitory effect due to their hydrogen bonding potential. The study also reveals the influence of substituents on the binding capabilities and in turn inhibitory potential of different analogues.