Abiesatrines A–J: anti-inflammatory and antitumor triterpenoids from Abies georgei Orr

Abstract

A novel spiro-lanostane (abiesatrine A, 1) was isolated from the aerial parts of Abies georgei together with 9 new (abiesatrines B-J, 2-10) and 10 known triterpenes (11-20). The new structures were established by the extensive analysis of their spectroscopic data. The configuration of 1, featuring a unique spirolactone formed by C-13 and C-23 via oxygen-bridge, was confirmed by X-ray crystallography, and its biopathway was tentatively proposed. Among these isolates, compound 16 showed the strongest inhibitory activity against LPS-induced NO production in RAW264.7 macrophages (IC(50) = 8.9 microg mL(-1)). While compounds 1 and 20 exhibited potent anti-proliferative effects on QGY-7703 cells with IC(50) values of 9.3 and 7.6 microg mL(-1), respectively. Preliminary structure-activity relationship (SAR) investigations defined structural feature of the 24Z-olefinic bond key to the lanostane and cycloartane pharmacophore.

A new 3,4-seco-cycloartane from the leaves ofHopea odorataRoxb.

“…(Yang et al 2010). In addition, the co-occurrence of 2 with its putative biogenetic precursor, namely the cycloartane-type mangiferonic acid (3), should also be highlighted.…”

“…abiesatrine J or 3,4-seco-cycloart-4(28),24-diene-3,26-dioic acid (2) (Yang et al 2010), mangiferonic acid (3) (Zhang et al 2003), friedelin (4) (Akihisa et al 1992), epifriedelanol (5) (Salazar et al 2000) and b-amyrine (6) (Mahato & Kundu 1994)), as well as two tocopherol trimers IVa (7) and IVb (8) (Row et al 2007) (Figure 1). Structures of known compounds were determined by comparison of their spectral data with those previously reported in the literature.…”

“…These data suggested that 1 was a 3,4-seco-cycloartane type triterpene. Furthermore, comparison of the 13 C NMR spectrum of 1 with those of abiesatrine J (Yang et al 2010) 3 (isolated in the present study) and other structurally related 3,4-seco-cycloartanes (e.g. gardenoin H, coccinetane A, sootepin E (Sy & Brown 1999;Nuanyai et al 2009Nuanyai et al , 2011) showed that carbon resonances from C-1 to C-21 were almost superimposable and that these compounds differ from one another only in the nature of their eight carbon side chain, corresponding to the formula C 28 H 55 O 4 in the case of 1.…”

Chemical constituents of Abies fabri

“…Hz) between H-15 and H-16 indicated the configuration of 15-OH was b-oriented(Yang et al, 2010b). The olefinic bond was deduced as being in an E-stereochemistry on the basis of the chemical shifts of H-24 at d H 6.90 and H 3 -26 at d H 1.84(Yang et al, 2010b).…”

“…Hz) between H-15 and H-16 indicated the configuration of 15-OH was b-oriented(Yang et al, 2010b). The olefinic bond was deduced as being in an E-stereochemistry on the basis of the chemical shifts of H-24 at d H 6.90 and H 3 -26 at d H 1.84(Yang et al, 2010b). The NOESY correlations of Me-18/H-19, H-19/Me-29, and Me-29/H-3 suggested the b-orientations of these protons, while the cross-peak of Me-30/H-17 suggested the a-orientations of Me-30 and H-17.…”