Lipase-catalyzed preparation of chromomycin A₃ analogues and biological evaluation for anticancer activity

Bioorg Med Chem Lett. 2012 Jul 1;22(13):4310-3. doi: 10.1016/j.bmcl.2012.05.015. Epub 2012 May 11.

Abstract

Several acyl derivatives of the aureolic acid chromomycin A(3) were obtained via lipase-catalyzed acylation. Lipase B from Candida antarctica (CAL-B) was found to be the only active biocatalyst, directing the acylation regioselectively towards the terminal secondary hydroxyl group of the aglycone side chain. All new chromomycin A(3) derivatives showed antitumor activity at the micromolar or lower level concentration. Particularly, chromomycin A(3) 4'-vinyladipate showed 3-5 times higher activity against the four tumor cell lines assayed as compared to chromomycin A(3).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acylation
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Biocatalysis
  • Candida / enzymology
  • Cell Line, Tumor
  • Chromomycin A3 / analogs & derivatives*
  • Chromomycin A3 / chemical synthesis
  • Chromomycin A3 / toxicity
  • Drug Screening Assays, Antitumor
  • Humans
  • Lipase / metabolism*
  • Mice
  • NIH 3T3 Cells
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Chromomycin A3
  • Lipase