Caffeic acid oligomers from Origanum dictamnus and Satureja pilosa as selective inhibitors of carbonic anhydrases: structure elucidation, X-ray crystallography

In the present study four depsides were isolated from Origanum dictamnus L. and Satureja pilosa Velen [ 1 ] [ 2 ] and were fully characterized spectroscopically by means of 1D- and 2D- NMR, HRMS and Circular Dichroism analyses. Experimental ECD measurements and ECD calculations confirmed the absolute configuration of salvianolic acid P 2 to be (8′R,7′′S,8′′S) [ 1 ]. Despite the absolute configuration of the newly reported dittanic acid 1 could not be determined, due to its superior molecular complexity and flexibility, the consistency between ECD spectra of 1 and 2 suggested the stereogenic centers being identical in both compounds. All NPs 1-4 ([ Fig. 1 ]) inhibited in vitro the tumor associated isoforms hCA IX and XII in low micromolar concentration ranges and with high degree of selectivity over the constitutive hCAs I and II. X-ray crystallography on the hCA II/salvianolic acid P 2 adduct demonstrated that the ligand established a multitude of stabilizing interactions within the catalytic cleft. Specifically, the two catechol moieties were engaged in hydrogen bonds with the ZBW and the DW placed at the bottom of the cavity as well as with aminoacids defining the rim of the active site. Finally, compounds 1-4 were assayed for their cytotoxicity on a prototypic human triple negative breast cancer cell line MDA-MB-231 and exerted significant cytotoxic effects. Although the mechanisms of action of 1-4 are likely to ascribe to a multitude of targets, our results strongly suggest that this class of oligomeric depsides is indeed a promising group of phenolic compounds worth of further investigation. Fig. 1 Structures of compounds 1-4 Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany