Tuning the Lewis acid phenol ortho-prenylation as a molecular diversity tool.

A diversity-oriented approach for the synthesis of various structurally different prenylated alcohols from readily accessible and common precursors was developed. With varying approaches, this article describes some successful examples of a Friedel-Crafts alkylation using methoxyphenols and different prenyl alcohols (geraniol and (E,E)-farnesol). We demonstrated that just by varying the stoichiometry of the Lewis acid used, the course of the reaction can be shifted to produce the alkylated or the cyclized product. Eighteen unique products were obtained with good isolated yields by direct alkylation with or without a consecutive π-cationic cyclization.

Convenient synthesis of the immunogenic glycolipid BbGL1.

A simple and efficient method to synthesize the immunogenic glycolipid BbGL1 is introduced. Two simple steps were required to obtain the desired product in good yield. First, a highly efficient glycosylation of cholesterol using galactosyl trichloroacetimidate as a donor was performed to produce cholesteryl-ß-d-galactoside. Finally, an efficient palmitoylation on the C6-OH of the galactose of the synthesized saponin using sym-collidine and acyl chloride under microwave heating that produced BbGL1 in good yield. The procedure is a convenient and cheaper alternative to the reported procedures allowing a rapid preparation of multiple analogs and conjugates.

Antitrypanosomal and antileishmanial activity of prenyl-1,2,3-triazoles.

A series of prenyl 1,2,3-triazoles were prepared from isoprenyl azides and different alkynes. The dipolar cycloaddition reaction provided exclusively primary azide products as regioisomeric mixtures that were separated by column chromatography and fully characterized. Most of the compounds displayed antiparasitic activity against Trypanosoma cruzi and Leishmania donovani. The most active compounds were assayed as potential TcCYP51 inhibitors.

Antifungal activity and cytotoxicity of extracts and triterpenoid saponins obtained from the aerial parts of Anagallis arvensis L.

ETHNOPHARMACOLOGICAL RELEVANCE: Anagallis arvensis L. (Primulaceae) is used in argentinean northwestern traditional medicine to treat fungal infections. We are reporting the isolation and identification of compounds with antifungal activity against human pathogenic yeast Candida albicans, and toxicity evaluation. AIM OF THE STUDY: to study the antifungal activity of extracts and purified compounds obtained form A. arvensis aerial parts, alone and in combinations with fluconazole (FLU), and to study the toxicity of the active compounds. MATERIALS AND METHODS: Disk diffusion assays were used to perform an activity-guided isolation of antifungal compounds from the aerial parts of A. arvensis. Broth dilution checkerboard and viable cell count assays were employed to determine the effects of samples and combinations of FLU + samples against Candida albicans. The chemical structures of active compounds were elucidated by spectroscopic analysis. Genotoxic and haemolytic effects of the isolated compounds were determined. RESULTS: Four triterpenoid saponins (1-4) were identified. Anagallisin C (AnC), exerted the highest inhibitory activity among the assayed compounds against C. albicans reference strain (ATCC 10231), with MIC-0 =1µg/mL. The Fractional Inhibitory Concentration Index (FICI=0.129) indicated a synergistic effect between AnC (0.125µg/mL) and FLU (0.031µg/mL) against C. albicans ATCC 10231. AnC inhibited C. albicans 12-99 FLU resistant strain (MIC-0 =1µg/mL), and the FICI=0.188 indicated a synergistic effect between AnC (0.125µg/mL) and fluconazole (16µg/mL). The combination AnC+ FLU exerted fungicidal activity against both C. albicans strains. AnC exerted inhibitory activity against C. albicans ATCC 10231 sessile cells (MIC50=0.5µg/mL and MIC80=1µg/mL) and against C. albicans 12-99 sessile cells (MIC50=0.75µg/mL and MIC80=1.25µg/mL). AnC exerted haemolytic effect against human red blood cells at 15µg/mL and did not exerted genotoxic effect on Bacillus subtilis rec strains. CONCLUSIONS: The antifungal activity and lack of genotoxic effects of AnC give support to the traditional use of A. arvensis as antifungal and makes AnC a compound of interest to expand the available antifungal drugs.