Guttiferones K and L, Antiproliferative Compounds of Rheedia calcicola from the Madagascar Rain Forest

Abstract

Bioassay-guided fractionation of the ethanol extract obtained from the fruits of Rheedia calcicola led to the isolation of two new guttiferone analogues, guttiferones K (1) and L (16-hydroxyguttiferone K) (2). The structures of 1 and 2 were established on the basis of extensive interpretation of one and two dimensional NMR spectroscopic data. Both compounds were tested for their antiproliferative activity against the A2780 human ovarian cancer cell line.As part of our continuing investigation of Madagascar plants for cytotoxic principles, 1 we found that an ethanol extract (MG 2796) of the fruits of Rheedia calcicola Jum. & H. Perrier (Clusiaceae) showed cytotoxicity in the A2780 assay with an IC 50 value of 15 µg/mL. This extract was selected for bioassay-guided fractionation based on its cytotoxicity against the A2780 human ovarian cancer cell line, and also on the absence of any previous chemical investigation of the species. Our bioassay-guided fractionation of Rheedia calcicola resulted in the isolation of two new cytotoxic guttiferone analogues, guttiferones K (1) and L (16-hydroxyguttiferone K) (2)The genus Rheedia has been found to be a rich sources of xanthones, 2-4 biflavonoids, 5-7 polyisoprenylated benzophenones (7-and 15-epiclusianone and xanthochymol), 7-9 and triterpenoids. 10 Their biological properties including brine shrimp lethality, 11 as well as antibacterial 10,11 and analgesic activity, 6 have been reported. 7-Epiclusianone and xanthochymol showed anti-HIV activity, 12 and xanthochymol also displayed antimicrobial activity 13 and cytotoxicity. 14 There is no information on traditional uses of the plant, and only lemurs eat its fruit. 15Extract MG 2796 was partitioned between hexane, CH 2 Cl 2 , and MeOH, and the CH 2 Cl 2 extract was found to be the most active with an IC 50 value of 10 µg/mL. The CH 2 Cl 2 extract was purified by filtration through a C18 cartridge followed by HPLC on a C18 column to yield compound 1 from the second fraction. Further HPLC separation of the first fraction using a C8 column yielded compound 2.*To whom correspondence should be addressed. Tel: (540) (Table 1) exhibited the presence of a 1,2,4-trisubstituted benzene ring. Four olefinic protons, one tertiary methyl and eight vinyl methyl groups, six methylenes, and one methine were also observed in the 1 H NMR and HSQC spectra of 1, indicating the presence of four 3-methylbut-2-enyl groups and a fifth C5 unit.The 13 C NMR spectrum of 1 ( (Figure 1) indicated the presence of two fragments, I (a 3,4-dihydroxybenzoyl group) and II (a 2,2-dimethylbicyclo[3.3.1]nonane ring system substituted with four 3-methylbut-2-enyl groups). The 1 H and 13 C NMR spectra of 1 were very similar to those of guttiferone A (3) 12b suggesting that 1 was a stereoisomer of guttiferone A. The correlations between CH 3 -22 and CH 2 -17/H-7α in the ROESY spectrum of 1 indicated that CH 3 -22 (δ H 0.81/δ C 16.4, in CD 3 OD/0.1%TFA) must be in the α-orientation like CH 2 -17. The 13 C NMR chemical shift of C-6 at δ C 42.0 in CD 3 OD/...

Complete assignment of the 1H and 13C NMR spectra of garciniaphenone and keto‐enol equilibrium statements for prenylated benzophenones

“…In this way, polyprenylated benzophenones are also known to possess free radical scavenging, [12] inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) expression inhibiting in colon carcinoma, [13] apoptosis induction, [14] antiulcer, [12] antioxidant, [15] trypanocidal, [16,17] cytotoxic, [18] antimicrobial, antifungal, [19] and antitumoral [20] properties. Furthermore, these compounds act as cancer chemopreventive, [21] antiproliferative to the A2780 human ovarian cancer cell line [22] and microtubule disassembly inhibitors. [23] One of the benzophenones reported in this study, 7-epi-clusianone, presents vascular effects on the rat aorta, [15] anti-HIV property [1] and in vitro activities against Artemia salina and trypomastigotes of Trypanosoma cruzi.…”

Qualitative and quantitative analysis of polycyclic polyprenylated acylphloroglucinols from Garcinia species using ultra performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry

“…1, 16 reference compounds, namely garcicowin D (1) [29], garcicowin C (2) [29], 30-epicambogin (3) [30], cambogin (4) [31], oblongifolin F (5) [20], oblongifolin G (6) [20], guttiferone K (7) [32], guttiferone F (8) [30], garciyunnanin B (9) [19], oblongifolin B (10) [33], garciyunnanin A (11) [19], oblongifolin A (12) [33], garcicowin B (13) [29], oblongifolin C (14) [33], guttiferone B (15) [30], and oblongifolin D (16) [33] were isolated from different Garcinia species in our laboratory and were identified by IR, UV, NMR spectroscopic analysis, and the purity of these authentic compounds was verified to be over 95% by HPLC-DAD and UPLC-MS detection. Each accurately weighed standard was dissolved in acetonitrile to give individual stock solutions.…”

Biodiversity conservation and drug discovery: Can they be combined? The Suriname and Madagascar experiences

“…Guttiferones of Rheedia calcicola Jum. & H. Perrier (Clusiaceae) from Madagascar showed mild activity against A2780 human ovarian cancer cell line (Cao et al, 2007a). Two xanthones were obtained from the Madagascar plant Terminalia calcicola H. Perrier (Combretaceae) (Cao et al, 2007b).…”