Four Diphenylpropanes and a Cycloheptadibenzofuran from Bussea sakalava from the Madagascar Dry Forest

Abstract

Investigation of the endemic Malagasy plant Bussea sakalava Du Puy & R. Rabev. (Fabaceae) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the four new diphenylpropanes 1-4 and the new cycloheptadibenzofuran 5; compound 5 has a previously unreported natural product skeleton. The structure elucidation of these compounds was based on the analysis of their 1D and 2D NMR and mass spectroscopic data. Compounds 1-5 were tested for antiproliferative activity against the A2780 human ovarian cancer cell line.In our continuing search for biologically active natural products from tropical rainforests as part of an International Cooperative Biodiversity Group (ICBG) program, we obtained an ethanol extract from the roots of a plant identified as Bussea sakalava Du Puy & R. Rabev. (Fabaceae) from Madagascar. This extract showed moderate antiproliferative activity against the A2780 human ovarian cancer cell line with an IC 50 value of 10 µg/mL. The extract was selected for examination on the basis of this activity and the absence of previous phytochemical studies of the species.Previous studies on the genus Bussea indicated the presence of azetidine-2-carboxylic acid and 3-hydroxyproline in seeds of different Bussea species,2 , 3 and the cytotoxicity and high trypanocidal activity of a methanol extract of stem bark of Bussea occidentalis has been reported.4Fractionation of a dichloromethane fraction of an ethanol extract of B. sakalava by C-18 open column and high performance liquid chromatography (HPLC) yielded four new diphenylpropanes named bussealins A-D (1 -4) and a cycloheptadibenzofuran derivative named bussealin E (5). Herein we report the structural elucidation of these new compounds and their antiproliferative properties against the A2780 human ovarian cancer cell line.* To whom correspondence should be addressed. Tel: (540) (Table 1) and were consistent with the molecular formula. The above data suggested that 1 had a diphenyl propane skeleton. The complete 1 H and 13 C NMR assignments and the connectivities were determined from analysis of a combination of COSY, HMQC, and HMBC data. Three mutually coupled methylene groups were revealed by the cross peaks observed in the COSY spectrum. In the HMBC spectrum, H-1 (δ H 2.41) showed correlations with C-2 (δ C 33.0), C-3 (δ C 30.6), C-1' (δ C 140.2), and with C-2' and C-6', both of which had the same chemical shifts (δ C 108.7). The A 2 substitution pattern of the A ring of 1 was established by HMBC correlations from the signal at δ H 6.18 (H-2' and H-6') to C-1 (δ C 36.5), C-1' (δ C 140.2), C-3' (δ C 151.3), C-4' (δ C 134.7) and C-6' and C-2' (δ C 108.7), as well as the correlation from one OCH 3 group at δ H 3.75 to C-4' (δ C 134.7). The proton substitutions on the B ring were assigned based on the 3 J HMBC correlations between H-3 (δ H 2.52) and C-6" (δ C 120.5), and between H-5" (δ H 6.38) and C-1" (δ C 123.4). Moreover, the H-5" proton showed HMBC correlations to C-6" (δ C 120.5), C-4" (δ C 147.8) and C-3" ...

Cardenolides of Leptadenia madagascariensis from the Madagascar dry forest

“…4 – 6 Previous phytochemical investigations reported the presence of flavonoids5,7,8 terpenoids1–10 polyoxypregnane esters,4,11 pregnane glycosides,12,13 cardiac glycosides14 and alkaloids15 in these species. The medicinal use of plants containing cardiac glycosides was recorded as early as 1500 years ago.…”

Antiplasmodial Sesquiterpenoid Lactones from Trichospira verticillata: Structure Elucidation by Spectroscopic Methods and Comparison of Experimental and Calculated ECD Data

“…33,34 The A2780 cell line is a drug-sensitive ovarian cancer cell line. 35 Paclitaxel was used as the positive control.…”

A Synthetic Butenolide Diterpene is now a Natural Product Isolated from Metaporana sericosepala, a Plant from the Madagascar Dry Forest [1a]

“…The A2780 ovarian cancer cell line assay was performed at Virginia Polytechnic Institute and State University as previously reported [9]. The A2780 cell line is a drug-sensitive ovarian cancer cell line [10].…”