Charles D. Hufford

Metabolism of antimalarial sesquiterpene lactones

Metabolism of artemisinin derivatives, which are antimalarial sesquiterpenes, appeared to lead to the production of the more polar metabolites in general. Presence of the endoperoxide moiety in the A/B ring structure seems crucial for the expression of antimalarial activity of these compounds. Microbial models served as effective predictors for the mammalian metabolism of artemisinin derivatives as well as producing quantities of metabolites for reference standards and structure elucidation studies. Combination of 2D-NMR and Thermospray HPLC/MS techniques was very useful for the structure elucidation of metabolites.

Antimicrobial properties of Honduran medicinal plants.

Ninety-two plants used in the traditional pharmacopoeia of the Pech and neighboring Mestizo peoples of central Honduras are reported. The results of in vitro antimicrobial screens showed that 19 of the extracts from medicinal plants revealed signs of antifungal activity while 22 demonstrated a measurable inhibitory effect on one or more bacterial cultures. Bioassay-guided fractionation of extracts from Mikania micrantha, Neurolaena lobata and Piper aduncum produced weak to moderately active isolates. The broad spectrum of activity of the extracts helps to explain the widespread use of these plants for wound healing and other applications.

3-Methoxysampangine, a novel antifungal copyrine alkaloid from Cleistopholis patens.

Further examination of the active ethanolic extract of the root bark of Cleistopholis patens by using bioassay-directed fractionation resulted in the isolation of a new alkaloid, 3-methoxysampangine (compound I), together with three known alkaloids, eupolauridine (compound II), liriodenine (compound III), and eupolauridine N-oxide (compound IV). The proposed structure of compound I was based on its physicochemical properties and spectral data. 3-Methoxysampangine exhibited significant antifungal activity against Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans. This is the first report of the isolation of liriodenine (compound III) from the root bark of C. patens.

NMR ASSIGNMENTS OF ELLAGIC ACID DERIVATIVES

HMBC spectroscopy optimized for small couplings was employed to determine the four‐bond and two‐bond proton carbon correlations on the aromatic rings of ellagic acid derivatives. Complete 13C NMR assignments of 3′‐O‐methyl‐3,4‐methylenedioxyellagic acid 4′‐O‐β‐D‐glucopyranoside (1), 3,3′‐di‐O‐methylellagic acid 4′‐O‐β‐D‐xylopyranoside (2), 3,3′,4‐tri‐O‐methylellagic acid 4′‐O‐β‐D‐glucopyranoside (3) and ellagic acid (4) were achieved using this technique. This study indicates that optimization of the delay time in the HMBC spectrum is crucial in assigning the 13C NMR signals of phenolic compounds with highly oxygenated quaternary carbons. Copyright

Triterpenes and flavonoids from Combretum leprosum

Abstract A new triterpene 3β,6β,16β-trihydroxylup-20(29)-ene, arjunolic acid, mollic acid, 3- 0 -methylquercetin and quercetrin were isolated from the leaves and roots of Combretum leprosum . The structures of these compounds have been determined by chemical and spectrometric methods, especially extensive 1D and 2D NMR experiments, including the use of the INADEQUATE technique for the new triterpene 3β,6β,16β-trihydroxylup-20(29)-ene.

Substituted Indoloquinolines as New Antifungal Agents

Cryptolepine (2) possesses desirable properties to serve as a lead in developing new antifungal agents. Using SAR techniques, several analogues of cryptolepine were designed to increase potency and to broaden the antifungal spectrum over several opportunistic microorganisms. A number of 2-substituted indoloquinolines have been synthesized and evaluated in antifungal screens and several have been shown to increase potency and expand the antifungal spectrum of cryptolepine. Comparison of MICs of a number of these analogues with standard antifungal agents, shows them to be comparable to Amphotericin B and Ketoconazole.

Clinic at the health food store? Employee recommendations and product analysis

Study Objectives. To determine what products health food store employees recommend for depression, to analyze the content of these products based on label claims, and to evaluate employee statements or recommendations for accuracy and safety.

Dihydrochalcones from Uvaria angolensis.

An investigation of the roots of Uvaria angolensis has led to the isolation and identification of two new dihydrochalcones, angoletin and uvangoletin, and the known C-benzyldihydrochalcones, uvaretin and isouvaretin. The structures were established from 13C NMR comparisons with known dihydrochalcones.

Structure elucidation and thermospray high-performance liquid chromatography/mass spectroscopy (HPLC/MS) of the microbial and mammalian metabolites of the antimalarial arteether

Microbial metabolism studies of the antimalarial drug arteether (1) have shown that arteether is metabolized to six new metabolites in addition to those previously reported (3). Large-scale fermentations with Cunninghamella elegans (ATCC 9245) and Streptomyces lavendulae (L-105) have resulted in the characterization of these metabolites primarily by two-dimensional nuclear magnetic resonance (2D-NMR) methods as 9β-hydroxyarteether (2), a ring rearrangement metabolite (3), 3α-hydroxy-11-epi-deoxydihydroartemisinin (4), 9α-hydroxyarteether (5), 2α-hydroxyarteether (6), and 14-hydroxyarteether (7). Thermospray mass spectroscopy/high-performance liquid chromatographic analyses have shown that four of these metabolites (2, 5, 6, 7) are also present in rat liver microsome preparations.

High-performance liquid chromatographic analysis of the metabolism of primaquine and the identification of a new mammalian metabolite.

Using rats that had been dosed with 20 mg/kg of primaquine diphosphate (11.4 mg/kg free base), it was found that the drug underwent a metabolic oxidative deamination to give 8-(3-carboxy-1-methylpropylamino)-6-methoxyquinoline. The presence of this new mammalian metabolite was verified using high-performance liquid chromatographic, gas chromatographic, and mass spectral methods. A quantitative high-performance liquid chromatographic method for the determination of primaquine and the carboxylic acid metabolite in plasma using only 50 microliters of whole blood from the rat was developed and the method could be used to detect levels as low as 0.05 microgram/ml of the metabolite. Following intravenous administration of the drug, it was found that the plasma levels of primaquine fell very rapidly and after 30 min, the levels of the metabolite were much higher than those of primaquine.