Anti-Staphylococcal and Cytotoxic Compounds from Hyptis pectinata

Bioassay-guided fractionation of a CHCl3 extract prepared from the Mexican medicinal plant Hyptis pectinata led to the isolation of four pyrones, pectinolides A - C (1 - 3) and H (4). Activity was tracked using cultured KB cells. Multidrug-resistant strains of Staphylococcus aureus were sensitive to pectinolide H (4; KB > 20 μg/mL) in the concentration range of 32 - 64 μg/mL. The absolute stereochemistry of this new compound was established as 5S-[(4S-acetyloxy)-(1S-hydroxy)-2Z-octenyl]-2(5H)-furanone on the basis of spectral, chiroptical data and chemical correlation with pectinolide A (1). Mosher ester derivatives were used with pectinolide B (2) for confirmation of the 3′-(S) absolute stereochemistry on the side chain chiral center of pectinolides A - C

Jalapinoside, a Macrocyclic Bisdesmoside from the Resin Glycosides of <i>Ipomea purga</i>, as a Modulator of Multidrug Resistance in Human Cancer Cells

The first macrocyclic bisdesmoside resin glycoside, jalapinoside (<b>4</b>), was purified by preparative-scale recycling HPLC from the MeOH-soluble extracts of <i>Ipomoea purga</i> roots, the officinal jalap. Purgic acid C (<b>3</b>), a new glycosidic acid of ipurolic acid, was identified as 3-<i>O</i>-β-d-quinovopyranoside, 11-<i>O</i>-β-d-quinovopyranosyl-(1→2)-<i>O</i>-β-d-glucopyranosyl-(1→3)-<i>O</i>-[β-d-fucopyranosyl-(1→4)]-<i>O</i>-α-l-rhamnopyranosyl-(1→2)-<i>O</i>-β-d-glucopyranosyl-(1→2)-<i>O</i>-β-d-quinovopyranoside (3<i>S</i>,11<i>S</i>)-dihydroxytetradecanoic acid. The acylating residues of this core were acetic, (+)-(2<i>S</i>)-methylbutanoic, and dodecanoic acids. The site of lactonization was defined as C-3 of the second saccharide moiety. Reversal of multidrug resistance by this noncytotoxic compound was evaluated in vinblastine-resistant human breast carcinoma cells

Modulators of antibiotic activity from Ipomoea murucoides

Reinvestigation of the CHCl3-soluble extract from the flowers of Ipomoea murucoides, through preparative-scale recycling HPLC, yielded three pentasaccharides of 11-hydroxyhexadecanoic acid, murucoidins XVII-XIX, in addition to the known murucoidin III and V, all of which were characterized by NMR spectroscopy and mass spectrometry. These compounds were found to be macrolactones of the known pentasaccharides simonic acid B and operculinic acid A. The acylating groups corresponded to acetic, (2S)- methyl-butyric, (E)-cinnamic and octanoic acids. The esterification sites were established at the C-2 of the second rhamnose and C-3 and C-4 of the third rhamnose. The aglycone lactonization was placed at C-2 or C-3 of the first rhamnose. Bioassays for modulation of antibiotic activity were performed against multidrug-resistant strains of Staphylococcus aureus, Escherichia coli Rosetta-gami, and two nosocomial pathogens: Salmonella enterica sv. Typhi and Shigella flexneri. The tested glycolipids did not act as cytotoxic (IC 50 > 4 μg/mL) nor as antimicrobial (MIC ≥ 128 μg/mL) agents. However, they exerted a potentiation effect on clinically useful antibiotics against the tested bacteria by increasing their antibiotic susceptibility up to four-fold at concentrations of 25 μg/mL

Structural elucidation and evaluation of multidrug-resistance modulatory capability of amarissinins A–C, diterpenes derived from Salvia amarissima

"Three new diterpenes (amarissinins A-C, 1–3) containing several oxygenated functionalities were isolated from the leaves and flowers of Salvia amarissima. The structures of these compounds were established through the analysis of their NMR spectroscopy and mass spectrometry data. The structures of compounds 1 and 2 were confirmed by single crystal X-ray diffraction. Compound 2was identified as a C-10 epimer of dugesin F (5). The cytotoxic activity of these compounds against five human cancer cell lines was determined. Additionally, the capability to modulate the multidrug resistance (MDR) in the MCF-7 cancer cell line resistant to vinblastine was tested.

Inhibitors of Bacterial Multidrug Efflux Pumps from the Resin Glycosides of Ipomoea murucoides⊥

A reinvestigation of the CHCl3-soluble extract from flowers of the Mexican medicinal arborescent morning glory, Ipomoea murucoides, through preparative-scale recycling HPLC, yielded six new pentasaccharides, murucoidins VI−XI (1−6), as well as the known pescaprein III (7), stoloniferin I (8), and murucoidins I−V (9−13). Their structures were characterized through the interpretation of their NMR spectroscopic and FABMS data. Compounds 1−6 were found to be macrolactones of three known glycosidic acids identified as simonic acids A and B, and operculinic acid A, with different fatty acids esterifying the same positions, C-2 on the second rhamnose unit and C-4 on the third rhamnose moiety. The lactonization site of the aglycone was placed at C-2 or C-3 of the second saccharide unit. The esterifying residues were composed of two short-chain fatty acids, 2-methylpropanoic and (2S)-methylbutyric acids, and two long-chain fatty acids, n-dodecanoic (lauric) acid and the new (8R)-(−)-8-hydroxydodecanoic acid. For the latter residue, its absolute configuration was determined by analysis of its Mosher ester derivatives. All members of the murucoidin series exerted a potentiation effect of norfloxacin against the NorA overexpressing Staphylococcus aureus strain SA-1199B by increasing the activity 4-fold (8 µg/mL from 32 µg/mL) at concentrations of 5−25 µg/mL. Stoloniferin I (8) enhanced norfloxacin activity 8-fold when incorporated at a concentration of 5 µg/mL. Therefore, this type of amphipathic oligosaccharide could be developed further to provide more potent inhibitors of this multidrug efflux pump

Characterization of a xylose containing oligosaccharide, an inhibitor of multidrug resistance in Staphylococcus aureus, from Ipomoea pes-caprae

Pescaprein XVIII (1), a type of bacterial efflux pump inhibitor, was obtained from the CHCl3-soluble resin glycosides of beach morning glory (Ipomoea pes-caprae). The glycosidation sequence for pescaproside C, the glycosidic acid core of the lipophilic macrolactone 1 containing d-xylose and l-rhamnose, was characterized by means of several NMR techniques and FAB mass spectrometry. Recycling HPLC also yielded eight non-cytotoxic bacterial resistance modifiers, the two pescapreins XIX (2) and XX (3) as well as the known murucoidin VI (4), pecapreins II (6) and III (7), and stoloniferins III (5), IX (8) and X (9), all of which contain simonic acid B as their oligosaccharide core. Compounds 1-9 were tested for in vitro antibacterial and resistance-modifying activity against strains of Staphylococcus aureus possessing multidrug resistance efflux mechanisms. All of the pescapreins potentiated the action of norfloxacin against the NorA over-expressing strain by 4-fold (8 μg/mL from 32 μg/mL) at a concentration of 25 μg/mL

Teotihuacanin, a Diterpene with an Unusual Spiro-10/6 System from <i>Salvia amarissima</i> with Potent Modulatory Activity of Multidrug Resistance in Cancer Cells

Teotihuacanin (<b>1</b>), an unusual rearranged clerodane diterpene with a new carbon skeleton containing a spiro-10/6 bicyclic system, was isolated from the leaves and flowers of <i>Salvia amarissima</i>. Its structure was determined through spectroscopic analyses. Its absolute configuration was established by single-crystal X-ray diffraction. Compound <b>1</b> showed potent modulatory activity of multidrug resistance in vinblastine-resistant MCF-7 cancer cell line (reversal fold, RF_MCF‑7/Vin+ > 10703) at 25 μg/mL