Geneive E. Henry

Identification and bioactivities of resveratrol oligomers and flavonoids from Carex folliculata seeds.

Plants of the Carex genus (Family: Cyperaceae) have attracted recent attention as potential food additives because they contain high levels of bioactive polyphenols commonly found in plant foods. Seven compounds, which included two resveratrol oligomers and five flavonoids, were isolated from seeds of Carex folliculata L. (northern long sedge), a forage prevalent in the northern United States. The compounds were identified by (1)H and (13)C nuclear magnetic resonance and mass spectrometry data. The resveratrol oligomers were pallidol (1), a resveratrol dimer reported to be present in levels equivalent to those of resveratrol in red wine, and kobophenol A (2), a resveratrol tetramer with a unique 2,3,4,5-tetraaryltetrahydrofuran skeleton. The flavonoids were isoorientin (3), luteolin (4), quercetin (5), 3-O-methylquercetin (6), and rutin (7). Compounds were evaluated for antioxidant activity in the diphenylpicrylhydrazyl (DPPH) radical scavenging assay; cytotoxicity activity against human colon (HCT116, HT29) and breast (MCF7, MDA-MB-231) tumor cell lines; and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). The antioxidant activities of the flavonoids (3-7; IC(50) values ranging from 50 to 200 microM) were comparable to that of ascorbic acid (IC(50) = 60 microM) and superior to those of the resveratrol derivatives (1 and 2; IC(50) > 1000 microM) and butylated hydroxytoluene (BHT; IC(50) = 1500 microM), a commercial antioxidant. In the cytotoxicity and antibacterial bioassays, compounds 4 (IC(50) for HCT116 = 45 microM) and 6 (IC(50) for MRSA = 6.4 microM) were the most active, respectively. Therefore, given the wide availability and underutilization of C. folliculata, this forage may provide a source of bioactive compounds useful for nutraceutical purposes. Also, this is the first reported phytochemical investigation of C. folliculata.

PRENYLATED BENZOPHENONE DERIVATIVES FROM CARIBBEAN CLUSIA SPECIES (GUTTIFERAE). PLUKENETIONES B-G AND XEROPHENONE A

Abstract Six new prenylated benzophenone derivatives plukenetiones B-G (2–7) have been isolated from the fruits of the Barbadian plant Clusia plukenetii. These structures were elucidated by the use of 2D NMR spectroscopic methods. The regiochemistry of xerophenone A from Clusia portlandiana has been revised.

Resveratrol Oligomers Isolated from Carex Species Inhibit Growth of Human Colon Tumorigenic Cells Mediated by Cell Cycle Arrest

Research has shown that members of the Carex genus produce biologically active stilbenoids including resveratrol oligomers. This is of great interest to the nutraceutical industry given that resveratrol, a constituent of grape and red wine, has attracted immense research attention due to its potential human health benefits. In the current study, five resveratrol oligomers (isolated from Carex folliculata and Carex gynandra ), along with resveratrol, were evaluated for antiproliferative effects against human colon cancer (HCT-116, HT-29, Caco-2) and normal human colon (CCD-18Co) cells. The resveratrol oligomers included one dimer, two trimers, and two tetramers: pallidol (1); α-viniferin (2) and trans-miyabenol C (3); and kobophenols A (4) and B (5), respectively. Although not cytotoxic, the resveratrol oligomers (1-5), as well as resveratrol, inhibited growth of the human colon cancer cells. Among the six stilbenoids, α-viniferin (2) was most active against the colon cancer cells with IC(50) values of 6-32 μM (>2-fold compared to normal colon cells). Moreover, α-viniferin (at 20 μM) did not induce apoptosis but arrested cell cycle (in the S-phase) for the colon cancer but not the normal colon cells. This study adds to the growing body of knowledge supporting the anticancer effects of resveratrol and its oligomers. Furthermore, Carex species should be investigated for their nutraceutical potential given that they produce biologically active stilbenoids such as α-viniferin.

Plukenetione A. An unusual adamantyl ketone from Clusia plukenetii (guttiferae)

Abstract The structure of plukenetione A from Clusia plukenetii Urban has been shown by spectroscopic methods to be 1-benzoyl-8,8-dimethyl-3,5-bis(3-methyl-2-butenyl)-6-(2-methylpropenyl)tricyclo[3.3.1.1 3,7 ]decane-2,4,9-trione.

Sensitivity of nonuniform sampling NMR.

Many information-rich multidimensional experiments in nuclear magnetic resonance spectroscopy can benefit from a signal-to-noise ratio (SNR) enhancement of up to about 2-fold if a decaying signal in an indirect dimension is sampled with nonconsecutive increments, termed nonuniform sampling (NUS). This work provides formal theoretical results and applications to resolve major questions about the scope of the NUS enhancement. First, we introduce the NUS Sensitivity Theorem in which any decreasing sampling density applied to any exponentially decaying signal always results in higher sensitivity (SNR per square root of measurement time) than uniform sampling (US). Several cases will illustrate this theorem and show that even conservative applications of NUS improve sensitivity by useful amounts. Next, we turn to a serious limitation of uniform sampling: the SNR by US decreases for extending evolution times, and thus total experimental times, beyond 1.26T2 (T2 = signal decay constant). Thus, SNR and resolution cannot be simultaneously improved by extending US beyond 1.26T2. We find that NUS can eliminate this constraint, and we introduce the matched NUS SNR Theorem: an exponential sampling density matched to the signal decay always improves the SNR with additional evolution time. Though proved for a specific case, broader classes of NUS densities also improve SNR with evolution time. Applications of these theoretical results are given for a soluble plant natural product and a solid tripeptide (u-(13)C,(15)N-MLF). These formal results clearly demonstrate the inadequacies of applying US to decaying signals in indirect nD-NMR dimensions, supporting a broader adoption of NUS.

A short synthesis of 5-methoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoic acid methyl ester

Abstract 5-Methoxy-2,2-dimethyl-2H-1-benzopyran-6-propanoic acid methyl ester was prepared in five steps and approximately 20% overall yield from 2,4-dihydroxybenzaldehyde. The two key reactions are the chromenylation between the unchelated hydroxyl group and C-3 of the resbenzaldehyde and the demethoxycarbonylation-alkylation of dimethyl malonate with a quaternary ammonium iodide.

Xerophenones A and B. New isoprenylated derivatives of 11-oxatricyclo[4.3.1.14,10]undecane-7,9-dione from Clusia portlandiana (Guttiferae)

Abstract A tautomeric pair of new isoprenylated benzophenone derivatives incorporating a novel oxatricyclic skeleton has been isolated from Clusia portlandiana Howard & Proctor and the structures and relative configuration established by NMR methods.

Bioactive acylphloroglucinols from Hypericum densiflorum.

Three acylphloroglucinol derivatives have been isolated from the hexane and acetone extracts of the aerial parts of Hypericum densiflorum Pursch. The compounds were characterized by NMR spectroscopy and mass spectrometry and identified as 4‐geranyloxy‐2,6‐dihydroxybenzophenone (1), 4‐geranyloxy‐1‐(2‐methylpropanoyl)‐ phloroglucinol (2) and 4‐geranyloxy‐1‐(2‐methylbutanoyl)‐phloroglucinol (3). Compounds 1–3 were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF‐7), lung (NCI H460), CNS (SF‐268), stomach (AGS) and colon (HCT‐116) tumor cell lines; antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA); inhibition of cyclooxygenase (COX‐1 and ‐2) enzymes; and antioxidant activity in the lipid peroxidation (LPO) assay. All three compounds showed moderate to strong antitumor, antibacterial, antioxidant and inhibition of COX‐2 activities. Also, this is the first reported occurrence of compound 3 in the Hypericum genus. Copyright

Acylphloroglucinol derivatives from Hypericum prolificum

Three new acylphloroglucinol derivatives have been isolated from the hexane extract of the aerial parts of Hypericum prolificum L.: prolificin A (1), prolifenone A (2), and prolifenone B (3). The structures were elucidated on the basis of extensive 2D NMR and MS data. All three compounds were evaluated for in vitro cell proliferation inhibitory activity against human breast (MCF-7), lung (NCI-H460), CNS (SF-268), stomach (AGS), and colon (HCT-116) tumor cell lines. Prolificin A showed growth inhibition of all cell lines with IC50 values ranging from 23 to 36 microM. Prolifenones A and B were inactive at the concentrations tested.

Inhibition of bacterial growth and biofilm production by constituents from Hypericum spp.

Biofilm embedded bacterial pathogens such as Staphylococcus spp., Escherichia coli, Pseudomonas aeruginosa, and Acinetobacter baumannii are difficult to eradicate and are major sources of bacterial infections. New drugs are needed to combat these pathogens. Hypericum is a plant genus that contains species known to have antimicrobial properties. However, the specific constituents responsible for the antimicrobial properties are not entirely known, nor have most compounds been tested as inhibitors of biofilm development. The investigation presented here tested seven secondary metabolites isolated from the species Hypericum densiflorum, Hypericum ellipticum, Hypericum prolificum, and Hypericum punctatum as inhibitors of bacterial growth and biofilm production. Assays were conducted against Staphylococcus epidermidis, Staphylococcus aureus, clinical methicillin‐resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii. Five of the seven compounds demonstrated growth inhibition against the Gram‐positive bacteria with minimum inhibitory concentrations (MIC) ranging from 1.95 µg/mL to 7.81 µg/mL. Four of the secondary metabolites inhibited biofilm production by certain Gram‐positive strains at sub‐MIC concentrations. Copyright