Eliane Garo

Asiatic acid and corosolic acid enhance the susceptibility of Pseudomonas aeruginosa biofilms to tobramycin.

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.

Five flavans from Mariscus psilostachys

Phytochemical investigation of two batches of Mariscus psilostachys led to the isolation and characterization of five flavans and three flavanones. Two flavans are new natural products and their structures have been established as (2S)-4′-hydroxy-5,7,3′-trimethoxyflavan and (±)-5,4′-dihydroxy-7-3′-dimethoxyflavan. Absolute configuration of the optically active compound isolated has been determined on the basis of its CD spectrum. Antimicrobial activity against Candida albicans and Cladosporium cucumerinum were determined for all compounds. The less polar flavans showed to be more active in both TLC assays and dilution assays.

Antibacterial clerodane diterpenes from Goldenrod (Solidago virgaurea).

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.

Isolation of apoptosis-inducing stilbenoids from four members of the Orchidaceae family.

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.

Isoflavones from Psorothamnus arborescens via high-throughput natural product chemistry methods

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.

Laxanol, a new 2,5-diaryl-3,4-dihydroxymethyltetrahydrofuran type lignan from Justicia laxa

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.

Dammarane-type triterpene glycosides from Oncoba manii active against methicillin-resistant Staphylococcus aureus.

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).