Antiproliferative Xanthones of Terminalia calcicola from the Madagascar Rain Forest

Abstract

A bioassay-guided fractionation of the EtOH extract of the Madagascan plant Terminalia calcicola H. Perrier (Combretaceae) led to the isolation of two new cytotoxic xanthones, termicalcicolanone A (1) and termicalcicolanone B (2). The structures of the new compounds were established on the basis of one and two dimensional NMR spectroscopic data. Both compounds showed modest antiproliferative activity toward the A2780 human ovarian cancer cell line.In our continuing search for bioactive molecules from the Madagascar rainforests as part of an International Cooperative Biodiversity Group (ICBG) program, 1 we obtained extracts of various parts of the tree Terminalia calcicola H. Perrier (Combretaceae) collected in Madagascar. The EtOH extract of the immature fruit proved to have moderate antiproliferative activity, with an IC 50 value of 14 µg/mL against the A2780 human ovarian cancer cell line. This extract was thus selected for bioassay-guided fractionation based on its cytotoxicity and also on the absence of any previous detailed phytochemical studies on this species.Previous phytochemical studies have revealed the genus of Terminalia to be a rich source of secondary metabolites, such as lignans, 2 flavonoids, 3 terpenoids, 4 and tannins. 5 Some of these metabolites have shown a wide range of biological activities, including anti-HIV-1, 2 antimalarial, 2 antifungal, 2,4 antibacterial, 4,6 and cytotoxic 5 activities. The anthelminthic and haemolytic properties of the terpene esters from T. macroptera have been studied. 4 The antioxidant effects of aqueous extract of T. chebula have also been investigated. 7Activity-guided fractionation of the dichloromethane extract (IC 50 , 10 µg/mL) by passage over a C18 open column, followed by purification of active fractions using C18 HPLC, led to the isolation of the two new compounds, 1 and 2. Table 1, including one carbonyl group, two aromatic rings with six oxygenated carbons, and two prenyl groups. The H-1″ resonance appeared at δ H 4.68, which was a more deshielded value than that usually found for this functionality, due to the effect of the C-9 carbonyl group. 9 Clearly, both the C-1 hydroxy and the C-8 3-methyl-but-2-enyl groups were peri to the carbonyl group. The ortho coupled aromatic H-5 and H-6 showed 3 J HMBC correlations (Figure 1) to C-7 and C-8a, and C-8 and C-10a, respectively, while H-1″ correlated to C-7, C-8, C-8a, C-2″, and C-3″, which provided further evidence for the position of the 3-methyl-but-2-enyl group at C-8. The HMBC correlations between the hydrogen-bonded proton (1-OH) and C-1, C-2, and C-9a, H-1′ and C-1, and H-2′ and C-2 were also observed, indicating that the 3′,3′-dimethylpyrano ring was fused at C-2 and C-3, which was confirmed by a ROESY correlation between the hydrogenbonded proton and H-1′. Based on the molecular formula of 1, the remaining two hydroxy groups must be located at C-4 and C-7, respectively. Thus, the structure of 1 was determined to be 5,8,12Termicalcicolanone B (2) was also obtained as a yellow powder. It was ...

Antiproliferative compounds ofArtabotrys madagascariensisfrom the Madagascar rainforest

“…The A2780 ovarian cancer cell line assay was performed on compounds 1-4 at Virginia Polytechnic Institute and State University as previously described [26].The A2780 cell line is a drug-sensitive human ovarian cancer cell line [27]. Key 2D NMR correlations of 1.…”

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 New Bioactive Diterpene Glycoside from Molinaea Retusa from the Madagascar Dry Forest

“…Assay was performed at Virginia Tech according to specifications previously described [5]. The A2780 cell line is a drug-sensitive ovarian cancer cell line [6].…”