Binding properties of sodium glucose co-transporter-2 inhibitor empagliflozin to human serum albumin: spectroscopic methods and computer simulations

Abstract

Empagliflozin is an oral sodium glucose co-transporter-2 inhibitor for type 2 diabetes mellitus. The interaction between empagliflozin and human serum albumin (HSA) was investigated experimentally and theoretically. Fluorescence quenching and time-resolved fluorescence spectroscopy indicated that the quenching mechanism of empagliflozin and HSA was dynamic and that the effective binding constant at body temperature was 3.495 × 10³ M⁻¹. Thermodynamic parameters showed that hydrophobic forces were the major binding force in the interaction between empagliflozin and HSA. Circular dichroism, Fourier transform infrared, and 3 D fluorescence spectroscopy revealed that empagliflozin showed a slight change in secondary structure without changing the basic carbon framework of HSA. Site marker displacement experiments revealed that empagliflozin bound to site I of HSA, which was supported by molecular docking. Molecular dynamic simulations indicated that empagliflozin could bind to HSA stably. This study provided insights into the binding mechanism between empagliflozin and HSA.

Communicated by Ramaswamy H. Sarma

Keywords:

• Human serum albumin (HSA)
• empagliflozin
• dynamic quenching
• spectroscopic methods
• molecular dynamic simulations
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (No. 21808020), the Applied Basic Research Project of Sichuan Province (Grant No. 2018JY0151）