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

Abstract

Glipizide is known to stimulate insulin secretion by β-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 10⁵ 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 α-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

Keywords:

• Glipizide
• human serum albumin
• molecular docking
• molecular dynamics
• circular dichroism

Acknowledgments

The authors are thankful to Dr. Tarique Sarwar, Department of Biosciences, Jamia Millia Islamia, New Delhi, India for experiments and critical review of the manuscript. The authors, Dr. Shafiul Haque & Dr. Razique Anwer are grateful to Jazan University and Imam Mohammad Ibn Saud Islamic University, Saudi Arabia, respectively, for providing the access of the Saudi Digital Library facility for this research study.

Authors’ contributions

Conceived and designed the study and experiments: RA, KIA, SH, NA, TF; Performed the experiments: RA, NA, SH, PS; Analyzed the data: RA, KIA, NA, SH, PS, TF, SMA; Contributed reagents/materials/analysis tools: RA, KIA, NA, SH, PS, TF, SMA; Wrote the paper: RA, KIA, SH, PA, TF, SMA. All authors reviewed the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.