Asiatic Acid and Corosolic Acid Enhance the Susceptibility of Pseudomonas aeruginosa Biofilms to Tobramycin

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

Acetylated Dammarane-Type Bisdesmosides from <i>Combretum inflatum</i>

The first study of the chemical constituents of <i>Combretum inflatum</i> has resulted in the isolation of seven new acetylated dammarane-type bisdesmosides (<b>1</b>–<b>7</b>). 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 <b>1</b>–<b>7</b> were screened for inhibition of an <i>Escherichia coli</i> strain UTI89 biofilm, MRSA inhibition, and cytotoxicity in NCI-H460 human lung cancer cells. Compounds <b>3</b>–<b>7</b> reduced the growth of MRSA at 16 μg/mL by 71–45%, and compound <b>7</b> had an IC₅₀ value of 3.9 μM in NCI-H460

Cytotoxic and Antibacterial Beilschmiedic Acids from a Gabonese Species of <i>Beilschmiedia</i>

High-throughput natural products chemistry methods have facilitated the isolation of eight new (<b>1</b>–<b>8</b>) and two known (<b>9</b> and <b>10</b>) beilschmiedic acid derivatives from the leaves of a Gabonese species of <i>Beilschmiedia</i>. Compounds <b>3</b>–<b>10</b> 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 <i>Staphylococcus aureus</i>, respectively. This is the first report of cytotoxic activity for the endiandric/beilschmiedic acid class of compounds

Diterpenes from the Endangered Goldenrod <i>Solidago shortii</i>

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 <i>Solidago shortii</i> is one example of an endangered species native to the United States. From <i>S. shortii</i>, one known diterpene (<b>1</b>), two new diterpenes (<b>2</b> and <b>3</b>), and three new hydrolysis products (<b>4</b>–<b>6</b>) 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