Discovery of nontriterpenoids from the rot roots of Panax notoginseng with cytotoxicity and their molecular docking study and experimental validation

Abstract

Panax notoginseng (PN) is a well-known traditional Chinese medicine, with dammarane-type triterpenoid saponins characterized as major component and active ingredients, together with amino acids, flavonoids, polysaccharides, and polyacetylenes. The roots of PN are susceptible to root rot disease, which causes a huge loss and changes in the chemical components of this precious resource. In this study, sub-fractions of rot PN root extracts were preliminarily found to have admirable cytotoxicity on two human cancer cells. Further bioassay-guided isolation discovered nine new non-triterpenoids, including two novel N-methylacetamido-1-oxotetrahydropyrimidine alkaloids (1, 2), five 2H-furanones or 2H-pyranones (3–7), and two polyacetylenic alcohols (8, 9). Their structures were illuminated by extensive spectroscopic data, calculated ECD, and X-ray diffraction analysis. Among them, 3–7 were considered to be transformed from panaxatriol through the intermediates (8, 9). The new alkaloids (1, 2) displayed noteworthy cytotoxicity against five human cancer cells with IC₅₀ values ranging from 14 to 24 μM. In silico target prediction and molecular docking studies showed that 1 and 2 may interact with EGFR, and were verified by the experimental inhibitory effect on EGFR tyrosine kinase.