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

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 (-) 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 H NMR, C NMR, and HRMS, and the spatial structure of compound was confirmed using X-ray crystallography. The biological results showed that some derivatives, including , , and , exhibited potent diuretic activity, and and displayed promising litholytic activity. Molecular docking studies further suggested that had an optimal binding affinity to WNK1 kinases related to diuresis, while 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.