Imines and lactones derived from friedelanes and their cytotoxic activity

Nat Prod Res. 2020 Mar;34(6):810-815. doi: 10.1080/14786419.2018.1508137. Epub 2018 Nov 2.

Abstract

Friedelan-3-one (1) and friedelane-3,16-dione (2) isolated from leaves and branches of Maytenus robusta Reissek were subjected to structural modifications via nucleophilic addition to the carbonyl group and Baeyer-Villiger oxidation in order to synthesize potential cytotoxic compounds. The oximes friedelane-3-hydroxyimino (3) and 3-hydroxyiminofriedelan-16-one (4) together with the lactones friedelane-3,4-lactone (5) and 3,4-lactonefriedelan-16-one (6) were characterized by IR and NMR spectroscopic analyses. Compounds 4 and 6 are reported for the first time. Cytotoxic screening via MTT assay in human leukemia cell lines (THP-1 and K562) demonstrated no significant improvement of compounds 3-6 when compared to the starting materials. Only compounds 3 and 5 demonstrated an improvement against K562 cells. However, the same assay on ovarian and breast cancer cell lines (TOV-21G and MDA-MB-231) showed a reduction in the IC50 for compounds 4-6, indicating that ring A modifications may enhance the biological potential.

Keywords: K562 cell line; Pentacyclic triterpenes; THP-1 cell line; TOV-21G cell line and MDA-MB-231 cell line; cytotoxicity property; friedelane derivatives.

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Celastraceae / chemistry*
  • Cell Line, Tumor
  • Cytotoxins / chemical synthesis
  • Cytotoxins / isolation & purification*
  • Cytotoxins / pharmacology
  • Humans
  • Imines / chemical synthesis
  • Imines / chemistry*
  • Lactones / chemical synthesis
  • Lactones / chemistry*
  • Plant Leaves / chemistry
  • Structure-Activity Relationship
  • Triterpenes / chemistry*
  • Triterpenes / isolation & purification

Substances

  • Antineoplastic Agents
  • Cytotoxins
  • Imines
  • Lactones
  • Triterpenes
  • friedelane