Unravelling the interaction of glipizide with human serum albumin using various spectroscopic techniques and molecular dynamics studies

Glipizide is known to stimulate insulin secretion by beta-cells of the pancreas. It is a second-generation sulfonylurea drug used in the management of type 2 diabetes. The shorter biological half-life makes it a suitable candidate to be designed as a controlled release formulation. Human serum albumin (HSA), a major plasma protein plays a crucial role in the transportation of drugs, hormones, fatty acids, and many other molecules and determines their physiological fate and biodistribution. In this study, the interaction of glipizide with HSA was investigated under physiological conditions using multi-spectroscopic techniques corroborated with molecular docking and dynamics approach. It was found that glipizide integrates to HSA with a binding constant in the order of 10(5) M-1. The mode of fluorescence quenching by glipizide is static in nature with one binding site. Glipizide preferentially interacts with sub-domain IIA of HSA and their complexion is thermodynamically favorable. This interaction results in the loss of alpha-helical content of HSA. The energy transfer efficiency from HSA to glipizide was found to be 26.72%. In silico molecular docking and simulation studies ratified in vitro findings and revealed that hydrogen bonds and hydrophobic interactions are accountable for glipizide-HSA complex formation. Communicated by Ramaswamy H. Sarma

Automated summary

Glipizide was found to have a high binding constant with human serum albumin (HSA) and exhibits static quenching mode with only one binding site. It interacts preferentially with sub-domain IIA of HSA and is thermodynamically favorable. This interaction results in a decrease in the alpha-helical content of HSA.