Foegraecumoside O and P, a Pair of Triterpenoid Saponins with a 4/5/6 Fused Tricyclic Oleanane Carbon Skeleton from Lysimachia foenum-graecum Hance

Abstract

Lysimachia foenum-graecum Hance (Primulaceae) is a medicinal plant used for cold, pain, ascariasis, etc., in China. Triterpenoid saponins have been found to be the main components of this genus. In this work, a pair of oleanane-type triterpenoid saponins with an unprecedented 4/5/6 fused tricyclic skeleton, foegraecumoside O (1) and foegraecumoside P (2) were isolated from the butanol fraction of the aerial parts of L. foenum-graecum. Their structures were determined using chemical methods and extensive spectroscopic analyses, along with quantum chemical calculations. Compound 2 displayed moderate cytotoxicity against HepG2, MGC-803, T24, NCI-H460, A549, and A549/CDDP (drug-resistant lung-cancer cell line) with IC₅₀ at 12.4-19.2 μM in an MTT assay, comparing with the positive control doxorubicin, which had IC₅₀ at 0.53-4.92 μM, but was inactive for A549/CDDP. Furthermore, a possible biosynthetic pathway for forming compounds 1 and 2 was proposed.

Keywords: Lysimachia; Lysimachia foenum-graecum; Primulaceae; cytotoxicity; triterpenoids.

Figure 1

Chemical structures of compounds 1 and 2.

Figure 2

The key COSY, HMBC, and NOESY correlations of compound 1.

Figure 3

Key NOESY correlations of compound 2.

Figure 4

Linear regression fitting of computed ¹³C NMR chemical shifts of compounds 1 (A,C) and 2 (B,D), with experimental values of compounds 1 (A,B) and 2 (C,D).

Figure 5

Linear regression fitting of computed ¹H NMR chemical shifts of compounds 1 (A,C) and 2 (B,D), with experimental values of compounds 1 (A,B) and 2 (C,D).

Scheme 1

Hypothetical biogenetic pathway for compounds 1 and 2.