Semisynthesis, Biological Evaluation and Molecular Docking Studies of Barbatic Acid Derivatives as Novel Diuretic Candidates

Abstract

Barbatic acid, a compound isolated from lichen, has demonstrated a variety of biological activities. In this study, a series of esters based on barbatic acid (6a–q′) were designed, synthesized, and evaluated for their diuretic and litholytic activity at a concentration of 100 μmol/L in vitro. All target compounds were characterized using 1H NMR, 13C NMR, and HRMS, and the spatial structure of compound 6w was confirmed using X-ray crystallography. The biological results showed that some derivatives, including 6c, 6b′, and 6f′, exhibited potent diuretic activity, and 6j and 6m displayed promising litholytic activity. Molecular docking studies further suggested that 6b′ had an optimal binding affinity to WNK1 kinases related to diuresis, while 6j could bind to the bicarbonate transporter CaSR through a variety of forces. These findings indicate that some barbatic acid derivatives could be further developed into novel diuretic agents.

Constituents of Chimaphila japonica and Their Diuretic Activity

“…WNK1 kinase was employed to evaluate the diuretic effects of selected compounds by docking them into the active site of the WNK1 kinase domain (PDB ID 5DRB) [ 24 ]. WNK463 was re-docked to the active site to validate docking reliability.…”

“…To explore the interaction between different compounds and the WNK1 kinase, the crystal structure of the WNK1 kinase domain in complex with WNK463 (PDB ID 5DRB) was selected to perform molecular docking studies [ 24 ]. Using the PubChem database ( , accessed on 5 January 2024) for the 2D structure of small molecule ligands, the 2D structures were fed into Chem Office 2022 software to produce their 3D structures.…”