2, 4, 5-Trideoxyhexopyranosides derivatives of diphyllin: Synthesis and anticancer activity

Chem Biol Drug Des. 2022 Aug;100(2):256-266. doi: 10.1111/cbdd.14095. Epub 2022 Jun 2.

Abstract

Diphyllin and its natural derivatives were identified as potent vacuolar H+ -ATPase (V-ATPase) inhibitors. In this study, twelve 2, 4, 5-trideoxyhexopyranosides derivatives of diphyllin were synthesized. Most of these compounds showed potent abilities to inhibit the growth of HT-29, MCF-7, HepG2 cancer cells with IC50 values at submicromolar concentration. The compounds 5c3 and 5c4 showed the best inhibitory activity on breast cancer cell lines MCF-7 with IC50 values of 0.09 and 0.10 μM. Compounds 5c3 and 5c4 showed similar V-ATPase inhibitory potency to diphyllin. Molecular docking showed that a hydrogen bond was found between the hydroxyl of 5c3 and SerA534 in the pocket of the V-ATPase receptor.

Keywords: 2, 4, 5-trideoxyhexopyranosides; V-ATPase inhibitor; diphyllin; molecular docking; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Benzodioxoles / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Lignans* / chemistry
  • Molecular Docking Simulation
  • Molecular Structure
  • Structure-Activity Relationship
  • Vacuolar Proton-Translocating ATPases* / metabolism

Substances

  • Antineoplastic Agents
  • Benzodioxoles
  • Lignans
  • Vacuolar Proton-Translocating ATPases
  • diphyllin