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

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.