Syntheses, cytotoxic activity evaluation and HQSAR study of 1,2,3-triazole-linked isosteviol derivatives as potential anticancer agents

Bioorg Med Chem Lett. 2016 Nov 15;26(22):5455-5461. doi: 10.1016/j.bmcl.2016.10.028. Epub 2016 Oct 13.

Abstract

A series of novel 1,2,3-triazole-linked isosteviol derivatives were designed and synthesized via Huisgen-click reaction. Their cytotoxicities in vitro against HCT-116 and JEKO-1 cells were screened. The preliminary bioassays indicated that most of the title compounds exhibited noteworthy cytotoxic activities. Particularly, the compound 10b revealed the most potent inhibitory activities against HCT-116 cells with IC50 value of 2.987±0.098μM, which was better than that (3.906±0.261μM) of positive control cisplatin. On the basis of these bioactivity data, hologram quantitative structure-activity relationship (HQSAR) was performed, and a statistically reliable model with good predictive power (r2=0.848, q2=0.544 and R2pred=0.982) was achieved. Additionally, the contribution maps derived from the optimal model explained the individual atomic contributions to the activity for each molecule.

Keywords: Click chemistry; Cytotoxicity; HQSAR; Isosteviol; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Survival / drug effects
  • Click Chemistry
  • Diterpenes, Kaurane / chemical synthesis
  • Diterpenes, Kaurane / chemistry*
  • Diterpenes, Kaurane / pharmacology*
  • Drug Screening Assays, Antitumor
  • HCT116 Cells
  • Humans
  • Models, Molecular
  • Neoplasms / drug therapy
  • Quantitative Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / chemistry*
  • Triazoles / pharmacology*

Substances

  • Antineoplastic Agents
  • Diterpenes, Kaurane
  • Triazoles
  • isosteviol