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

Arch Pharm (Weinheim). 2025 Jan;358(1):e2400823. doi: 10.1002/ardp.202400823.

Abstract

In this study, four depsides were isolated from Origanum dictamnus L. and Satureja pilosa Velen. medicinal plants and their structures were assessed by means of one-dimensional (1D)- and two-dimensional (2D)-nuclear magnetic resonance, high resolution mass spectrometry, and electronic circular dichroism analyses. The compound 1, herein reported for the first time, salvianolic acid P 2, clinopodic acid I 3, and clinopodic acid O 4 were all profiled in vitro on a panel of human (h) expressed carbonic anhydrases (CAs; EC 4.2.1.1) and preferential inhibition for the tumor-associated human carbonic anhydrase (hCA) IX and hCA XII over the constitutively expressed hCA I and hCA II isoforms was observed. X-ray crystallography allowed us to assess the binding mode of salvianolic acid P 2 to hCA II. The compounds exhibited significant cytotoxic effects on the human triple-negative breast cancer cell line MDA-MB-231, suggesting that this class of depsides are promising molecules for future investigation.

Keywords: Origanum dictamnus; Satureja pilosa; carbonic anhydrases; depsides; dittanic acid.

MeSH terms

  • Antineoplastic Agents, Phytogenic* / chemistry
  • Antineoplastic Agents, Phytogenic* / isolation & purification
  • Antineoplastic Agents, Phytogenic* / pharmacology
  • Carbonic Anhydrase Inhibitors* / chemical synthesis
  • Carbonic Anhydrase Inhibitors* / chemistry
  • Carbonic Anhydrase Inhibitors* / isolation & purification
  • Carbonic Anhydrase Inhibitors* / pharmacology
  • Carbonic Anhydrases* / isolation & purification
  • Carbonic Anhydrases* / metabolism
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Depsides* / chemistry
  • Depsides* / isolation & purification
  • Depsides* / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Origanum* / chemistry
  • Structure-Activity Relationship

Substances

  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrases
  • Depsides
  • Antineoplastic Agents, Phytogenic