Design and synthesis of novel quinic acid derivatives: in vitro cytotoxicity and anticancer effect on glioblastoma

Future Med Chem. 2020 Nov;12(21):1891-1910. doi: 10.4155/fmc-2020-0194. Epub 2020 Oct 30.

Abstract

Aim: Quinic acid (QA) is a cyclic polyol exhibiting anticancer properties on several cancers. However, potential role of QA derivatives against glioblastoma is not well established. Methodology & results: Sixteen novel QA derivatives and QA-16 encapsulated poly (lactic-co-glycolic acid) nanoparticles (QA-16-NPs) were screened for their anti-glioblastoma effect using standard cell and molecular biology methods. Presence of a tertiary hydroxy and silylether groups in the lead compound were identified for the antitumor activity. QA-16 have 90% inhibition with the IC50 of 10.66 μM and 28.22 μM for LN229 and SNB19, respectively. The induction of apoptosis is faster with the increased fold change of caspase 3/7 and reactive oxygen species. Conclusion: QA-16 and QA-16-NPs shows similar cytotoxicity effect, providing the opportunity to use QA-16 as a potential chemotherapeutic agent.

Keywords: PLGA; chemotherapeutic drugs; cytotoxicity; glioblastoma; nanoparticle; quinic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • Glioblastoma / drug therapy*
  • Glioblastoma / metabolism
  • Glioblastoma / pathology
  • Humans
  • Quinic Acid / chemical synthesis
  • Quinic Acid / chemistry
  • Quinic Acid / pharmacology*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Quinic Acid