Synthesis, cytotoxic evaluation, and molecular docking of novel zerumbone oxime esters and azazerumbone derivatives

Bioorg Med Chem Lett. 2025 May 1:120:130120. doi: 10.1016/j.bmcl.2025.130120. Epub 2025 Feb 1.

Abstract

Available online A series of thirteen novel zerumbone oxime esters and five new azazerumbone derivatives were successfully synthesized. Most of these derivatives exhibited significant cytotoxic activity against four human tumor cell lines (HepG2, A549, HL-60, and AGS). Among them, three derivatives (3i, 3j, and 3k) demonstrated strong cytotoxic effects against all tested cell lines, with IC50 values ranging from 0.41 ± 0.05 to 3.88 ± 0.19 μg/mL, displaying potency comparable to that of zerumbone and ellipticine. Docking results revealed that one compound (3i) showed the highest binding affinity for NF-κB p65.

Keywords: Azazerumbone; Cytotoxicity; Humulenoid; Oxime-ester; Zerumbone.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor*
  • Esters* / chemical synthesis
  • Esters* / chemistry
  • Esters* / pharmacology
  • Humans
  • Molecular Docking Simulation*
  • Molecular Structure
  • Oximes* / chemical synthesis
  • Oximes* / chemistry
  • Oximes* / pharmacology
  • Sesquiterpenes* / chemical synthesis
  • Sesquiterpenes* / chemistry
  • Sesquiterpenes* / pharmacology
  • Structure-Activity Relationship

Substances

  • Oximes
  • Antineoplastic Agents
  • zerumbone
  • Sesquiterpenes
  • Esters