Sonochemical synthesis of 2-substituted nicotinic acid ethyl ester derivatives: Their in vitro and in silico evaluation against SIRT1

Abstract

Based on the initial docking studies of a representative compound in silico the evaluation of SIRT1 inhibitory potential of 2-substituted nicotinic acid ethyl ester derivatives was undertaken in vitro. A sonochemical method was developed and employed for the faster synthesis of this class of compounds. The methodology involved the iodine-mediated reaction of β-enamino esters with allylic alcohols in aqueous DMSO in the presence of air under mild conditions. A number of 2-substituted nicotinic acid ethyl ester derivatives were synthesized by employing this ultrasound assisted method in good to acceptable yield. The use of less expensive iodine and aqueous media, milder reaction condition and shorter reaction time are the key advantages of the current approach. All the synthesized compounds were tested for their SIRT1 inhibitory potential in vitro when some of them showed good activities and the compound 3g being the best among them. The docking studies suggested that the fused lactone ring of 3g played a key role in interacting with the SIRT1 in silico via formation of H-bonds. The overall outcome of the in vitro and in silico studies suggested the compound 3g as an initial hit molecule for further pharmacological studies.