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 ...
Antimalarial bioassay-guided fractionation of an EtOH extract of the root wood of Cryptocarya rigidifolia (Lauraceae) led to the isolation of the five new 5,6-dihydro-α-pyrones cryptorigidifoliols A–E (1–5) and the six bicyclic tetrahydro-α-pyrone derivatives cryptorigidifoliols F–K (6–11). The structure elucidations of all compounds were made on the basis of the interpretation of spectroscopic data and chemical derivatization, and the relative and absolute configurations were determined by NOESY, electronic circular dichroism (ECD), and 1H NMR analysis of α-methoxyphenylacetyl (MPA) derivatives. The bicyclic tetrahydro-α-pyrone derivatives were identified as products of acid-catalyzed intramolecular Michael addition of the 5,6-dihydro-α-pyrones in the presence of silica gel. A structure–activity relationship study suggested that the presence of an α,β-unsaturated carbonyl moiety is not essential for potent antimalarial activity.
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/...
The synthesis of a series of thiolated paclitaxel analogs is described as part of a novel nanomedicine program aimed at developing formulations of paclitaxel that will bind to gold nanoparticles for tumor targeted drug delivery. Preliminary evaluation of the new nanomedicine comprised of 27 nm gold nanoparticles, tumor necrosis factor alpha (TNFα), thiolated polyethylene glycol (PEG-Thiol) and one of several thiolated paclitaxel analogs is presented.
Bioassay-guided fractionation of an ethanol extract of the leaves and inflorescence of Mallotus oppositifolius collected in Madagascar led to the isolation of the two new bioactive dimeric phloroglucinols, mallotojaponins B (1) and C (2), together with the known mallotophenone (3). The structures of the new compounds were determined on the basis of spectroscopic evidence, including their 1- and 2D-NMR spectra, mass spectrometry, and an X-ray crystal structure. Compounds 1 and 2 showed potent antimalarial activity against chloroquine-resistant Plasmodium falciparum, with IC50 values of 0.75 ± 0.30 and 0.14 ± 0.04 μM, while 3 was inactive in this assay. Compounds 1–3 also displayed strong antiproliferative activity against the A2780 human ovarian cancer cell line (IC50 1.10 ± 0.05, 1.3 ± 0.1 and 6.3 ± 0.4 μM, respectively).
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" ...
Investigation of the South African plant Urginea depressa Baker (Asparagaceae Juss.) for antiproliferative activity against the A2780 ovarian cancer cell line led to the isolation of the six new homoisoflavonoids urgineanins A-F (1 - 6), the two known bufatrienolides 7 and 9, and the new bufatrienolides urginins B and C (8 and 10). Structures were elucidated based on analysis of their 1D and 2D NMR spectra, electronic circular dichroism, and mass spectrometric data. Five of the six new homoisoflavonoids had good antiproliferative activity against the A2780 ovarian cancer, A2058 melanoma, and H522-T1 human non-small cell lung cancer cells, and urgineanin A (1) had submicromolar activity against all three cell lines. The four bufatrienolides 7 – 10 had strong antiproliferative activity against the same cell line, with IC50 values of 24.1, 11.2, 111 and 40.6 nM, respectively.
A conformationally restrained epothilone A analogue (3) with a short bridge between methyl groups at C6 and C8 was designed and synthesized. Preliminary biological evaluation indicates 3 to be only weakly active (IC50 = 8.5 microM) against the A2780 human ovarian cancer cell line.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.