A New and Known Cytotoxic Aryltetralin-Type Lignans from Stems of Bursera graveolens

Abstract

The genus Bursera (in Burseraceae) comprises about 40 species distributed in tropical zones of Latin and South America. Some species in this genus are used as perfumes and folk medicines.1) Bursera graveolens HBK is a wild tree native from Mexico and Yucatan to Peru and Venezuela and has been used as a remedy for stomach ache, sudorific, and a liniment for rheumatism.2) In the previous paper, 3) we reported the isolation of luteolin 3Ј-O-a-L-rhamnopyranoside and three of its new acylated derivatives along with four known flavonol glycosides from leaves of B. graveolens, and the inhibitory activity of the isolated compounds for the Maillard reaction.In our continuing study on B. graveolens, we found that the MeOH extract from the stems showed a potent cytotoxic activity in in vitro assay (vide post). This finding prompted us to investigate the chemical components in the MeOH extract of the stems and, as a result, a new podophyllotoxin-like 4a-aryltetralin-type lignan termed burseranin (1) and a known analogous lignan picropolygamain (2) were isolated together with two known triterpenes. In the present report, we describe the isolation, the structural determination, and biological activity of the isolated compounds in detail. The MeOH extract was partitioned with AcOEt and water. The AcOEt soluble part was subjected to repeated separation by silica gel columns, followed by a Sep-Pak octadecyl silica gel (ODS) column to afford 1 and 2 together with known triterpenes, lupeol and epi-lupeol.Burseranin 1, a colorless waxy solid, gave the molecular ion peak at m/z 382 (M (Table 1). A carbon signal at d C 178.3, reasonably assigned to a g-lactone carbonyl carbon in the 13 C-NMR spectrum (Table 1), 4) in conjunction with detailed two dimensional (2D) analysis by the 1 H-1 H correlation spectroscopy (COSY), heteronuclear multiquantum coherence (HMQC), and heteronuclear multiple bond connectivity (HMBC) (Fig. 1), gave the podophillotoxin-like planar structure for 1 shown in Fig. 1. Furthermore, nuclear Overhauser enhancement spectroscopy (NOESY) correlations observed between H-4 and H-5 and between H-4 and H-2Ј also supported the validity of this established plane structure. The relative structure of 1 was determined based on the 1 H coupling constants (J values) and the NOESY data as follows. In 4-aryltetralin-type lignans having a fused 2,3-g-lactone moiety, the J 2,3 -values of the 2,3-cis-g-lactone derivatives were reported to be about 9.3-9.6 Hz and those of the 2,3-transg-lactone series about 14.8-15.5 Hz. [5][6][7][8][9] According to these reported data, the J 2,3 -value (9.5 Hz) of 1 suggested that 1 carries a 2,3-cis-g-lactone moiety in the molecule. Analogously, the J 3,4 -value (3.0 Hz) of 1 was consistent with the reported values for the 3,4-trans-configuration in 4-aryltetralin lignans with the 2,3-cis-g-lactone.6-9) Furthermore, the va- A new 4a a-aryltetralin-type lignan called burseranin (1) and a known analogous lignan picropolygamain (2) were isolated along with known triterpenes, lupeol and epi-lupeol f...

The Hexane Fraction of Bursera microphylla A Gray Induces p21-Mediated Antiproliferative and Proapoptotic Effects in Human Cancer–Derived Cell Lines

“…The phytochemical composition of BM hexane extract (BM-H) led to the isolation of several terpenoids, among which 3 were new (malabaricatrienol, malabaricatrienone, and microphyllanin), and of 4 known lignans—namely, burseran, ariensin, burseranin, and dihydroclusin acetate. 15 In view of the known cytotoxic activity of the isolated lignans, 14 - 16 we sought to test the antiproliferative activity of BM resin extract on the acute myeloid leukemia (AML) cell line OCI 1 because this cell line is positive for both p21 and p53, molecules critical for both proliferation and apoptosis. We also extended the study to other cancer-derived cell lines to determine the extract’s possible mechanism of action.…”

Cytotoxic Aryltetralin Lignans from Fruits of Cleistanthus indochinensis

“…3), in which the β-glucopyranose moiety was linked to C-3′ of the Aring, as indicated by an HMBC cross-peak of C-3′ at δ C = 144.4 with the anomeric proton H-1′′ at δ H = 4.67. The D-configuration for the glucopyranose moiety of 6 was assigned from the positive Analysis of the 1 H and 13 C NMR spectra of 7 revealed the same planar structure with burseranin, which was previously isolated from Bursera graveolens [14]. However, H-8′ of 7 presented small (J = 4.5 Hz) and strong (J = 14.0 Hz) coupling constants, whereas these values were J = 3.0 and 9.5 Hz for burseranin (C/D cis-fused junction).…”

Anti-inflammatory and antioxidative effects of six pentacyclic triterpenes isolated from the Mexican copal resin of Bursera copallifera

“…Pentacyclic triterpenes are commun metabolites in the resins of Bursera species. B. delpechiana contains principally triterpenes with ursan skeleton, including α-amyrin [26]; the stem of B. graveolens contain lignans, and the triterpenes lupeol and epilupeol [27], and the leaves produce flavonoids and the triterpene α-amyrin [28]; B. simaruba , synthesize lupene-related pentacyclic triterpenes such as lup-20(29)-en-3β,23-diol, lupeol, epilupeol, epiglutinol and α-amyrin [29–31]. Finally, B. microphylla was reported to have malabaricane type triterpenes [32].…”