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

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.

• Authors: Akshaya Murugesan, Suvi Holmstedt, Kenna C Brown, Alisa Koivuporras, Ana S Macedo, Nga Nguyen, Pedro Fonte, Patrícia Rijo, Olli Yli-Harja, Nuno R Candeias, Meenakshisundaram Kandhavelu
• Journal: Future medicinal chemistry (Future Med Chem) Vol. 12 Issue 21 Pg. 1891-1910 (11 2020) ISSN: 1756-8927 [Electronic] England
• PMID: 33124467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Quinic Acid

Topics

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