PhD Scientific Days 2023

Pharmaceutical Sciences II.

Cytotoxic Malonyl-Caffeoylquinic Acid and Malonyl-Flavonoid Derivatives from Two Edible Apiaceae Plants Anthriscus cerefolium and Chaerophyllum bulbosum

Text of the abstract

Introduction: Anthriscus cerefolium and Chaerophyllum bulbosum are closely related Apiaceae plants with medicinal and culinary importance, however their phytochemical composition is poorly investigated: Malonyl-dicaffeoylquinic acids in A. cerefolium were detected without confirming their isomeric structures and flavonoid-glycosides in both plants were identified without detecting their malonyl derivatives. Scientific validation for the safety of these herbs is still lacking. Aims and Methods: Current study was designed to 1) depict the accumulation of the compounds in various organs of A. cerefolium and C. bulbosum during a full vegetation cycle of one year by high-performance liquid chromatography coupled with high-resolution tandem mass spectrometry (HPLC-HR-MS/MS), 2) define optimum tissues and vegetation phases, allowing for the isolation of high-purity compounds, 3) determine the structures of the isolated compounds by nuclear magnetic resonance spectroscopy (NMR), and 4) evaluate the cytotoxic potential of the isolated compounds on various cancer cell lines (HT-29, HepG2, HL-60, U87, and A2058) in comparison to the normal kidney-derived epithelial cell line, Vero. Results: Dimalonyl-dicaffeoylquinic acid (DiMDiCQ) was identified in A. cerefolium and C. bulbosum for the first time. High-purity DiMDiCQ can be isolated from the early spring leaf of A. cerefolium and from the flowers of C. bulbosum collected in June, confirming a vegetation phase- and tissue-specific accumulation of this compound. Malonyl-dicaffeoylquinic acid (MDiCQ) was found to be the main compound in all samples of A. cerefolium and C. bulbosum. In addition to MDiCQ and DiMDiCQ, high amount of kaempferol malonylglucoside (KMG) was accumulated in the flowers of C. bulbosum, enabling the high-purity isolation of these compounds. MDiCQ and DiMDiCQ reduced the viability of the non-cancerous Vero cells (IC50 values were lower than 10 µM for both compounds). Conclusion: Our results show that malonyl-dicaffeoylquinic acids evoke toxicity on normal cells of the body hence, the use of these plants should be re-evaluated.
Funding: This work was supported by the National Research, Development and Innovation Office, Hungary (grants: OTKA NKFIH K-135712 and K-142904) and Tempus Foundation (Stipendium Hungaricum Scholarship).