Two new C(13) nor-isoprenoids from the leaves of Casearia sylvestris.

Two new C(13) nor-isoprene glycosides, (6S,9S)-6,9-dihydroxymegastiman-4-en-9-O-beta-D-glucopyranoside (1) and (6S,9S)-6,9-dihydroxymegastiman-4-en-9-O-beta-D-apiofuranosyl-(1-->6)-beta-D-glucopyranoside (2) were isolated from the leaves of Casearia sylvestris, along with icariside B(5) (3), byzantionoside B (4), blumenol B (5), blumenol C (6) and loliolide (7). The structures of these compounds were determined on the basis of 1D and 2D NMR, MS and circular dichroism (CD) spectroscopic analyses, chemical methods and comparison with the literature data.

Sorocenols G and H, anti-MRSA oxygen heterocyclic Diels-Alder-type adducts from Sorocea muriculata roots.

Bioassay-guided fractionation of a root extract of Sorocea muriculata led to the isolation and identification of two new oxygen heterocyclic Diels-Alder-type adducts, sorocenols G (1) and H (2), along with lupeol-3-(3' R-hydroxytetradecanoate) and oxyresveratrol. The structures of 1 and 2 were elucidated using 1D and 2D NMR spectroscopic and HRMS data and by comparison with reported values. The absolute configurations of 1 and 2 were established by analysis of their experimental and theoretically calculated CD spectra. Compounds 1 and 2 showed significant and selective activity against methicillin-resistant Staphylococcus aureus with IC50 values of 1.5 and 0.5 microM, respectively. Compound 2 also displayed antifungal activity against Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, with IC 50 values of 5.4, 5.4, and 10.0 microM, respectively.

Capisterones A and B, which enhance fluconazole activity in Saccharomyces cerevisiae, from the marine green alga Penicillus capitatus.

A whole-cell-based assay using Saccharomyces cerevisiae strains that overexpress Candida albicans CDR1 and MDR1 efflux pumps has been employed to screen natural product extracts for reversal of fluconazole resistance. The tropical green alga Penicillus capitatus was selected for bioassay-guided isolation, leading to the identification of capisterones A and B (1 and 2), which were recently isolated from this alga and shown to possess antifungal activity against the marine pathogen Lindra thallasiae. Current work has assigned their absolute configurations using electronic circular dichroism and determined their preferred conformations in solution based on detailed NOE analysis. Compounds 1 and 2 significantly enhanced fluconazole activity in S. cerevisiae, but did not show inherent antifungal activity when tested against several opportunistic pathogens or cytotoxicity to several human cancer and noncancerous cell lines (up to 35 microM). These compounds may have a potential for combination therapy of fungal infections caused by clinically relevant azole-resistant strains.

Phenolic glycosides from Potalia amara.

Investigation of the stem bark of the unique Amazonian herbal plant Potalia amara yielded two new phenolic glycosides, potalioside A (1) and B (2), along with di-O-methylcrenatin (3), 2,6-dimethoxy-4-hydroxyphenol 1-glucoside and sweroside. The structures of potalioside A and B were established by interpretation of spectral data as 4-hydroxymethyl-2,6-dimethoxyphenyl 1-O-beta-D-glucopyranosyl(1-->6)-beta-D-glucopyranoside and 4-hydroxymethyl-2,6-dimethoxyphenyl 1-O-beta- D-xylopyranosyl(1-->6)- beta-D-glucopyranoside, respectively.

Naturally occurring proteasome inhibitors from mate tea (Ilex paraguayensis) serve as models for topical proteasome inhibitors.

Proteasome inhibitors have emerged as a clinically important therapy for neoplastic disease, with velcade, an organoboron compound used extensively in multiple myeloma. Recently, (-)-epigallocatechin gallate has been found to be a potent inhibitor of the proteasomal chymotrypsin-like activity. Other compounds that inhibit angiogenesis and are active as chemopreventive agents, such as curcumin, also inhibit proteasome activity. We have screened natural product extracts using ras-transformed endothelial cells (SVR cells) as a bioassay, and found that extracts of mate tea (Ilex paraguayensis) inhibit the growth of these endothelial cells. The extract was fractionated and found to have novel cinnamate esters that inhibit proteasome activity. Based upon the structures of the compounds isolated from mate tea, we examined synthetic analogs of these compounds for proteasome activity. Cinnamic acid amides had no inhibitory activity against proteasomes, whereas cinnamate esters displayed the activity. Based upon these findings, preclinical and clinical trials of topical cinnamate esters as proteasome inhibitors are warranted for psoriasis and other inflammatory disorders.

Acetylenic acids inhibiting azole-resistant Candida albicans from Pentagonia gigantifolia.

Antifungal bioassay-guided isolation of the ethanol extract of the roots of Pentagonia gigantifolia yielded 6-octadecynoic acid (1) and the new 6-nonadecynoic acid (2). Compounds 1 and 2 inhibited the growth of fluconazole-susceptible and -resistant Candida albicans strains. Their antifungal potencies were comparable to those of amphotericin B and fluconazole. Of particular significance is the low cytotoxicity and specific activity of 1 and 2 against C. albicans.

Antimicrobial and antiparasitic (+)-trans-hexahydrodibenzopyrans and analogues from Machaerium multiflorum.

Machaerium multiflorum yielded two additional new (+)-trans-hexahydrodibenzopyrans (HHDBP's), machaeriol C (1) and machaeriol D (2), and three new 5,6-seco-HHDBP's, machaeridiol A (3), machaeridiol B (4), and machaeridiol C (5). Their structures and stereochemistries were determined by 1D and 2D NMR data, including HMBC, NOESY, and circular dichroism experiments. Machaeriol C (1) demonstrated in vitro antibacterial activity against Staphylococcus aureus (IC(50) 0.65 microg/mL) and methicillin-resistant S. aureus (MRSA) (IC(50) 0.70 microg/mL), while its corresponding 5,6-seco-analogues machaeridiol A (3) and machaeridiol B (4) showed antibacterial activity against S. aureus and MRSA (IC(50) 1.0-2.6 microg/mL) and antifungal activity against Candida albicans (IC(50), 2.0-3.5 microg/mL). In addition, machaeridiol B (4) demonstrated antiparasitic activities against Plasmodium falciparum D6 and W2 clones and Leishmania donavani with IC(50) values of 0.64, 0.22, and 0.9 microg/mL, respectively.

Flavanone glycosides from Miconia trailii.

Assay-guided fractionation of the ethanol extract of the twigs and leaves of Miconia trailii yielded two new flavanone glycosides, matteucinol 7-O-alpha-l-arabinopyranosyl(1-->6)-beta-d-glucopyranoside (miconioside A, 1) and farrerol 7-O-beta-d-apiofuranosyl(1-->6)-beta-d-glucopyranoside (miconioside B, 2), along with the known compounds matteucinol 7-O-beta-d-apiofuranosyl(1-->6)-beta-d-glucopyranoside (3), matteucinol (4), 2alpha,3beta,19alpha-trihydroxyolean-12-ene-24,28-dioic acid (bartogenic acid, 5), 2alpha,3beta,23-trihydroxyolean-12-ene-28-oic acid (arjunolic acid, 6), 2alpha,3alpha,19alpha, 23-tetrahydroxyurs-12-ene-28-oic acid (myrianthic acid, 7), and stigmast-4-ene-3,6-dione (8). The structures of 1-8 were elucidated by spectroscopic methods, including 2D NMR.