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 opportunity to use QA-16 as a potential chemotherapeutic agent.

Unveiling the multifaceted antiproliferative efficacy of Cichorium endivia root extract by dual modulation of apoptotic and inflammatory genes, inducing cell cycle arrest, and targeting COX-2

“… 120 Moreover, Murugesan et al observed the cytotoxic impact of quinic acid derivatives on human glioblastoma cell lines SNB19 and LN229. 121 Consequently, the list of bioactive metabolites detected in the CIR extract ( Table 1 ) aligns with the observed antiproliferative potential of the CIR extract against various types of cancer cells.…”

Methanol extraction revealed anticancer compounds Quinic Acid, 2(5H)‑Furanone and Phytol in Andrographis paniculata

“…Numerous flavonoids, terpenoids and polyphenols, are known to inhibit carcinogenesis and tumorigenesis in vivo and in vitro. Among the identified compounds 2(5H)-Furanone (86)(87)(88)(89) along with phytol (90,91) and QA (92,93) are used in the treatment of several types of cancer. Since it is the predominant component identified by GC-MS, it could be the predominant anticancer and anti-inflammatory component of the extracts.…”

Glioblastoma: Current Status, Emerging Targets, and Recent Advances

“…Murugesan et al proposed quinic acid derivatives as potential inhibitors of GBM cells. 98 A total of 16 quinic acid derivatives were synthesized and evaluated in LN229 and SNB19 cell lines, where 160 showed promising anti-proliferative activity, with IC 50 = 10.66 and 28.22 μM, respectively. Furthermore, 160 was formulated into nanoparticles, which showed a similar effect as 160 alone, and biological studies confirmed that 160 induces apoptosis through the ROS-mediated pathway and caspase 3/7 ( Figure 41 A).…”

“…Murugesan et al proposed quinic acid derivatives as potential inhibitors of GBM cells . A total of 16 quinic acid derivatives were synthesized and evaluated in LN229 and SNB19 cell lines, where 160 showed promising anti-proliferative activity, with IC 50 = 10.66 and 28.22 μM, respectively.…”

“…Studies discussed in this Perspective on dual MDM-2–TSPO inhibitors, dual HDAC1–LSD inhibitors, dual PDK1–aurora kinase inhibitors, dual RGD integrin–MDM protein inhibitors, and others − are expected to pave the way for the initiation of similar programs to expand the size of the anti-GBM pipeline. Notably, at the preliminary and preclinical levels, medicinal chemists have explored synthetic adducts as well as natural product libraries to furnish new chemical architectures for the treatment of GBM. − Imaging tools and chemical probes for GBM (radio-iodinated tracers with specificity to PARP-1, microtubules, 18 F-labeled radiotracers, carborane-containing boron dipyrromethenes, , and cyanine–gemcitabine) have also been generated. Moreover, many preliminary studies merely focusing on the cellular effects of the new scaffolds have also been included in this work. − Although mechanistic studies were not performed, the study results appear to be promising, and the pinpointed potent scaffolds can be subjects of future investigation.…”