One new and seven known diterpenes were identified from an antibacterial chromatographic fraction of Taxodium ascendens . Of these, demethylcryptojaponol ( 2 ), 6-hydroxysalvinolone ( 3 ), hydroxyferruginol ( 4 ), and hinokiol ( 5 ) demonstrated potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). These compounds represent a class of synthetically accessible compounds that could be further developed for treatment of drug-resistant bacterial infections.

One new and seven known diterpenes were identified from an antibacterial chromatographic fraction of Taxodium ascendens. Of these, demethylcryptojaponol (2), 6-hydroxysalvinolone (3), hydroxyferruginol (4), and hinokiol (5) demonstrated potent activity against clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). These compounds represent a class of synthetically accessible compounds that could be further developed for treatment of drug-resistant bacterial infections.

Species extinction is tantamount to loss of chemical diversity, and so it is important to seize all opportunities to study species on the brink of extinction. Such studies are often hampered by the limited material available, but that obstacle is surmountable through collaboration with botanical gardens and advances in instrumentation. The goldenrod Solidago shortii is one example of an endangered species native to the United States. From S. shortii, one known diterpene (1), two new diterpenes (2 and 3), and three new hydrolysis products (4-6) are described. This work was made possible through collaboration with the Missouri Botanical Garden and with the use of highly sensitive microcryoprobe NMR technology for structure elucidation and VCD spectroscopy for the determination of absolute configuration.

The first study of the chemical constituents of Combretum inflatum has resulted in the isolation of seven new acetylated dammarane-type bisdesmosides (1-7). Their structures were determined from microgram quantities on hand using Bruker BioSpin TCI 1.7 mm MicroCryoProbe technology, ESIMS, and comparison to data found in the literature. Compounds 1-7 were screened for inhibition of an Escherichia coli strain UTI89 biofilm, MRSA inhibition, and cytotoxicity in NCI-H460 human lung cancer cells. Compounds 3-7 reduced the growth of MRSA at 16 μg/mL by 71-45%, and compound 7 had an IC₅₀ value of 3.9 μM in NCI-H460.

High-throughput natural product research produced a suite of anticancer hits among several species of the Orchidaceae family (Oncidium microchilum, O. isthmi, and Myrmecophila humboldtii). A commercial Oncidium sp. was also examined as a convenient source of additional material. Isolation and structure elucidation led to the identification of fifteen stilbenoids including a new phenanthraquinone and two new dihydrostilbenes. NMR data for structure elucidation and dereplication were acquired utilizing a Bruker BioSpin TCI 1.7-mm MicroCryoProbe or a 5-μL CapNMR capillary microcoil. Several compounds inhibited proliferation of NCI-H460 and M14 cancer cell lines. All compounds were also examined for their ability to induce apoptosis. Apoptosis induction was determined by measuring caspase 3/7 activation and LDH release in a NCI-H460 cell line. Based on these results, a portion of the extract from a commercially available Oncidium sp. was chemically modified in an attempt to obtain additional phenanthraquinones.

High-throughput natural products chemistry methods have facilitated the isolation of eight new (1-8) and two known (9 and 10) beilschmiedic acid derivatives from the leaves of a Gabonese species of Beilschmiedia. Compounds 3-10 were isolated in microgram quantities, and the NMR data for structure elucidation and dereplication were acquired utilizing a Bruker BioSpin TCI 1.7 mm MicroCryoProbe. All of the compounds were screened for cytotoxic and antibacterial activity against NCI-H460 human lung cancer cells and a clinical isolate of methicillin-resistant Staphylococcus aureus, respectively. This is the first report of cytotoxic activity for the endiandric/beilschmiedic acid class of compounds.

A high-throughput phytochemical investigation of Abronia villosa afforded a new rotenoid designated abronione (1) along with the known compounds boeravinone C and lupeol. The structure of 1 was determined using NMR, MS, and optical analysis with < 400 µg of material. Compound 1 displayed moderate cytotoxicity against NCI-H460 and HL-60 human cancer cell lines with IC(50) values of 14 and 36 µM, respectively.

A phytochemical investigation of Monanthotaxis congoensis afforded eight polyoxygenated cyclohexenes as well as the known crotepoxide. Structures were determined using NMR, MS, and optical rotation analyses. One compound displayed moderate antiproliferative activity against NCI-H460 and M14 cancer cells.

High-throughput natural products chemistry methods have led to the isolation of three new (1-3) and two known indole sesquiterpene alkaloids (4, 5) from Greenwayodendron suaveolens. Their structures were determined using CapNMR and MS. Pentacyclindole (1) was determined to possess a new natural product framework. Pentacyclindole (1) and polyalthenol (4) showed activity against clinical isolates of Staphylococcus aureus with polyalthenol (4) demonstrating a MIC(90) of 4 microg/mL.

Bioassay‐guided fractionation of the antibacterial ethyl acetate‐ethanol (50 : 50) extract obtained from the aerial parts of Penstemon centranthifolius led to the isolation of six phenylethanoid glycosides (1–6) and eleven iridoid glycosides (7–17). Their structures were determined on the basis of spectroscopic analysis and comparison with the literature. Among them, two phenylethanoid glycosides, 4″′‐O–acetylverbascoside (1) and verbascoside (2), were found to show significant inhibition of the formation of bacterial biofilms by Escherichia coli UTI89. Compound 1 showed 77% biofilm inhibition at 2.5 µg/mL, and compound 2 showed 60% inhibition at 5 µg/mL. Copyright © 2009 John Wiley & Sons, Ltd.

Nine clerodane diterpenes, solidagoic acids C-I (1-7), cleroda-3,13(14)-dien-16,15:18,19-diolide (8) and cleroda-3,13(14)-dien-15,16:18,19-diolide (9) were isolated and characterised from the ethanol-ethyl acetate (1:1) extract of Solidago virgaurea. The structures were determined by NMR spectroscopic analysis. Several displayed moderate antibacterial activity against Staphylococcus aureus. (C) 2009 Elsevier Ltd. All rights reserved.

The new secoiridoid glycoside alatenoside (6) was isolated along with the known secoiridoid glycosides morroniside (1), (7 alpha)-7-O-methylmorroniside (2), (7 beta)-7-O-methylmorroniside (3), alpigenoside (4). and kingiside (5). Complete NMR data for 2. 3, and 4 are presented here for the first time. The structure elucidation and de-replication of the isolates were performed by utilizing a capillary-scale NMR probe and HR-ESI-MS data. Alatenoside (6) represents the first naturally occurring morroniside dimer.

Drug-resistant bacteria are becoming more prevalent both in the community and in hospitals. In a search for new antibiotic leads, we used a high-throughput natural products chemistry approach to isolate one new (1) and two known (2, 3) dammarane-type triterpenes with mass-limited material from the African plant Oncoba manii. The new compound was determined by spectroscopic methods to be 1beta,2alpha,3beta,20(R)-tetrahydroxydammar-24-ene 3-O-alpha-L-rhamnopyranosyl-(1 --> 2)-beta-D-glucopyranoside. Compounds 1 and 2 inhibited the growth of methicillin-resistant Staphylococcus aureus (MRSA).

The unsymmetrical 2,5-diaryl-tetrahydrofuran type lignan, 2-(3′-methoxy-4′-hydroxyphenyl)-3,4-dihydroxymethyl-5-(3″-methoxy-5″-hydroxyphenyl)-tetrahydrofuran, laxanol (1), was obtained from Justicia laxa via high-throughput natural product chemistry methods as a mass-limited sample and its structure was elucidated by capillary scale NMR and HR-/LR-ESIMS analyses.

One new 3′,4′,5′,5,7-pentahydroxy-2′,2‴-bis-dihydrobiflavonol, acuminatanol (1), was obtained from the aqueous extract of Trichoscypha acuminata. The structure elucidation process was performed primarily utilizing a capillary scale NMR probe. Acuminatanol (1) is the first example of a bis-dihydroflavonol linked exclusively via the B-rings at C-2′ and C-2‴ positions. To date, it is the first naturally-occurring compound reported from the genus Trichoscypha, and the first new natural product published from our compound libraries generated from the aqueous extracts of American and African plants.

ABSTRACT Asiatic acid and corosolic acid are two natural products identified as biofilm inhibitors in a biofilm inhibition assay. We evaluated the activities of these two compounds on Pseudomonas aeruginosa biofilms grown in rotating disk reactors (RDRs) in combination with tobramycin and ciprofloxacin. To determine the ruggedness of our systems, the antibiotic susceptibilities of these biofilms were assessed with tobramycin and ciprofloxacin. The biofilm bacteria produced in the RDR were shown to display remarkable tolerance to 10 μg/ml of ciprofloxacin, thus mimicking the tolerance observed in recalcitrant bacterial infections. These studies further demonstrate that a nonmucoid strain of P. aeruginosa can form a biofilm that tolerates ciprofloxacin at clinically relevant concentrations. Neither asiatic acid nor corosolic acid reduced the viable cell density of P. aeruginosa biofilms. However, both compounds increased the susceptibility of biofilm bacteria to subsequent treatment with tobramycin, suggesting asiatic acid and corosolic acid to be compounds that potentiate the activity of antibiotics. A similar statistical interaction was observed between ciprofloxacin and subsequent treatment with tobramycin.

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One new isoflavone, arborestin (2), together with the known fremontin (1), were obtained from Psorothamnus arborescens via high-throughput natural product chemistry methods. The isoflavones were isolated and the structure elucidation was performed using a capillary scale NMR probe and HR-/LR-ESIMS data.

Three species of Phragmipedium (Orchidaceae), P. calurum, P. longifolium, and P. hybrid (var. Sorcerer's Apprentice), were analyzed by high-throughput isolation. A total of 12 new (1-4, 6-10, 12, 14, 16) and five known compounds (5, 11, 13, 15, 17) were isolated from these orchids. Compounds 1-8 are stilbenes substituted with one or two 4-hydroxybenzyl moieties. This type of substitution on stilbenes is unusual and has been reported only twice. The structure elucidation was based on spectroscopic analysis.

Five new (1-5) and four known (6-9) C14-oxygenated 1alpha-hydroxy-11(13)-pseudoguaien-6beta,12-olides with potent inhibition of hepatitis C virus (HCV) replication were obtained from Parthenium hispitum via high-throughput natural product chemistry methods. A semipreparative HPLC system was used to purify these compounds. The miniaturization of the structure elucidation and dereplication for the mass-limited samples were performed primarily utilizing a capillary-scale NMR probe. Compounds 2-4 were found to possess in vitro anti-HCV activity in the subgenomic HCV replicon system containing luciferase reporter with significant inhibition above 90% at 2 microM concentration.