Chebulinic and chebulagic acid binding with serum proteins: biophysical and molecular docking approach

Abstract

Chebulinic acid (CHN) and chebulagic acid (CHG) have been known for centuries for their anti-cancer, anti-diabetes, HIV and anti-inflammatory properties. In this study, the interaction of these phytochemicals CHN/CHG, with the two major transport proteins for various drugs, human serum albumin (HSA) and α-1-acid glycoprotein (AGP), was unraveled by using several spectroscopic techniques and computational methods. The binding of CHN/CHG quenches the HSA/AGP fluorescence intensities, and also these phytochemicals are bound strongly to HSA/AGP proteins. An apparent decrease in fluorescence intensities of CHN/CHG-HSA and CHN/CHG-AGP complex showed the static mode of fluorescence quenching. Furthermore, the intrinsic fluorescence and using site-specific markers ibuprofen competing with these molecules, thereby replacing it in the binding site of subdomain IIIA. The computational methods substantiated the experimental findings, revealing that CHN interacted with Lys414A, Glu492A, Glu492A and Lys413A residues of subdomain IIIA of HSA and for CHG showed the interaction with Lys545A and Lys413A residues of subdomain IIIA of HSA. Fluorescence and surface plasmon resonance data unveiled a previously unreported binding event between CHN/CHG and HSA; the determined binding affinities of both compounds were slightly higher for HSA than AGP. A change in functionality of protein confirmed the esterase‐like activity of HSA in the presence of CHG/CHN upon binding with CHG/CHN. Displacement and circular dichroism (CD) experiments analysis showed that the two CHN/CHG and binding specifically to IIIA subdomain on HSA results in the conformational changes in the HSA. Thus, CD revealed a few conformational changes in HSA due to CHN/CHG. The binding of these two phytochemicals to the plasma proteins would give a path to develop new inspired drug molecules for chronic diseases.

Communicated by Ramaswamy H. Sarma

Keywords:

• α-1-acid glycoprotein
• docking
• human serum albumin
• surface plasmon resonance
• fluorescence emission
• phytochemical

Acknowledgments

We thank Bioinformatics facilities, University of Hyderabad.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Science and Engineering Research Board (SB/EMEQ-064/2014 dated 14-07-2015) and UPE-2 University of Hyderabad. RS also thank the infrastructural grants provided by DST-FIST, UGC-SAP and Builder-DBT-BT/INF/22/SP41176/2020, India. .