ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

Inhibition of PTP1B by isosinensetin, a polymethoxylated flavone isolated from trifoliate orange peel: kinetic studies, molecular docking, and molecular dynamics simulation

Nguyen Minh Trang, Le Ba Vinh, Nguyen Van Thanh, and Nguyen Viet Phong

Institute of Marine Biochemistry (IMBC), Vietnam Academy of Science and Technology (VAST), Hanoi, Vietnam

E-mail: ngvietphong@gmail.com

Received: 13 June 2022  Accepted: 22 October 2022

Abstract:

The development of novel therapeutic and preventative strategies is needed to attenuate the expansion of type 2 diabetes. Here, modern spectroscopy techniques including high-resolution mass spectrometry, 1D, and 2D NMR were used to determine the chemical structure of isosinensetin (ISO) isolated from the ethanol extract of trifoliate orange peel. ISO exhibited the protein tyrosine phosphatase 1B (PTP1B) inhibitory activity with the IC₅₀ value of 2.61 ± 0.14 µM and acted as a noncompetitive inhibitor against PTP1B with a K_i value of 0.92 ± 0.06 µM. ISO can bind to the allosteric site of PTP1B with a binding affinity value of − 7.1 kcal/mol, as demonstrated by molecular docking simulations, and the results are consistent with kinetic investigations. In addition, to study the behavioral and dynamic characteristics of the protein–ligand complex, molecular dynamics simulation for ISO was performed. The in silico ADME prediction revealed that ISO was a good drug-like candidate. Therefore, trifoliate orange and ISO have therapeutic potential for use in treating type 2 diabetes.

Keywords: Isosinensetin; Protein tyrosine phosphatase 1B; Kinetic; Molecular docking; Molecular dynamics

Full paper is available at www.springerlink.com.

DOI: 10.1007/s11696-022-02560-y

Chemical Papers 77 (3) 1751–1757 (2023)