Synthesis, cytotoxic activity, and 2D- and 3D-QSAR studies of 19-carboxyl-modified novel isosteviol derivatives as potential anticancer agents

Chem Biol Drug Des. 2017 Jun;89(6):870-887. doi: 10.1111/cbdd.12910. Epub 2017 Feb 2.

Abstract

Two series of novel acylthiosemicarbazide and oxadiazole fused-isosteviol derivatives were synthesized based on the 19-carboxyl modification. The target compounds were evaluated for their cytotoxicities against three cancer cell lines (HCT-116, HGC-27, and JEKO-1) using an MTT assay. Lead compounds from the acylthiosemicarbazides (4) showed IC50 values in the lower micromolar range. For example, compounds (4i, 4l, 4m, 4r, and 4s) exhibited significant inhibitory activities against the three cell lines with IC50 values of 0.95-3.36 μm. Furthermore, 2D-HQSAR and 3D-topomer CoMFA analyses were established, which could be used to develop second generation of isosteviol derivatives as anticancer agents.

Keywords: 2D-HQSAR; 3D-topomer CoMFA; cytotoxicity; isosteviol derivatives; synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Computer Simulation*
  • Diterpenes, Kaurane / chemical synthesis*
  • Diterpenes, Kaurane / chemistry
  • Diterpenes, Kaurane / pharmacology*
  • HCT116 Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Neoplasms / drug therapy
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry
  • Oxadiazoles / pharmacology
  • Quantitative Structure-Activity Relationship
  • Semicarbazides / chemical synthesis
  • Semicarbazides / chemistry
  • Semicarbazides / pharmacology

Substances

  • Antineoplastic Agents
  • Diterpenes, Kaurane
  • Oxadiazoles
  • Semicarbazides
  • isosteviol
  • thiosemicarbazide