Synthesis of New Indole‐Based Thiazole Derivatives as Potential Antiglycation and Anti α‐Glucosidase Agents: In Vitro and In Silico Studies

Abstract

AbstractDiabetes mellitus is a metabolic disease, characterized by the elevated levels of blood glucose, known as hyperglycemia. It is one of the serious health challenges, and is rapidly becoming a significant cause of morbidity, and mortality, worldwide. The persistent hyperglycemic state in diabetes mellitus leads to the formation of advanced glycation end products (AGEs), which is identified as a key factor involved in the progression of diabetes, and diabetes‐associated late complications. keeping in view the medicinal properties of indole, and thiazole, in the present study, novel indole‐based thiazoles (1–26) were synthesized, and evaluated for their in vitro α‐glucosidase, and antiglycation activities. These indole‐based thiazoles were characterized from their spectral data. All these compounds showed moderate to excellent antiglycation activity (IC50 between 642.2±0.013 to 46.93±0.003 μM) including compounds 17, 20, 22–26 which showed a significant antiglycation activity as the reference molecule, rutin (IC50=56±0.008 μM) used as standard. Further, these derivatives exhibited significant α‐glucosidase inhibition activity (P<0.001) with IC50 in the range of 111.8±0.9001 and 666.5±1.0111 μM (standard drug acarbose: IC50=855.8±1.2001 μM). Binding interactions of these compounds with α‐glucosidase enzyme were studied in silico, which showed strong correlation with the experimental data. Inhibition of α‐glucosidase enzyme, and AGEs formation by these compounds suggest them as promising scaffolds for further studies.