Development of pH-adjusted NMR methodology for quantitation of caffeoylquinic acid derivatives and evaluation of their antimalignant pleural mesothelioma potential

Journal of Pharmaceutical and Biomedical Analysis 2025 July 15 [Link]

Hau Thi Hong Bui, Yoon-Jin Lee, Trung Huy Ngo, Punam Thapa, Yun-Seo Kil, Chang Yeol Lee, Hyukjae Choi, Kyu Joon Lee, Joo-Won Nam

Abstract

Quantitative analysis of caffeoylquinic acids (CQAs) is challenging due to their structural similarities and susceptibility to isomerization and degradation. To overcome these limitations, a pH-adjusted quantitative 1H NMR (qHNMR) method is proposed for evaluating different CQAs in the extracts using a MeOD/HEPES-d18 buffer. This method was applied to measure the concentrations of chlorogenic acid (1) and 3,5-di-CQA (4) in Cuscuta japonica extract, and of chlorogenic acid (1) in green coffee bean extracts. A comparison of quantum mechanics (QM)-based and non-quantum mechanics-based approaches in qHNMR has shown that the application of QM-qHNMR improves the precision and sustainability of quantitative NMR. In addition, C. japonica extract and its isolated CQAs (1-7) were investigated for anticancer effects against NCI-H2452 cells, showing that methyl di-CQA esters (5 and 7) inhibit proliferation and induce apoptosis of NCI-H2452 cells, indicating their potential as therapeutic agents for treating malignant pleural mesothelioma.