Inhibitory effects of maesanin and analogs on arachidonic acid metabolizing enzymes.

The substituted 1,4-benzoquinone, maesanin (1), is a potent 5-lipoxygenase (5-LO) inhibitor present in the fruit of Maesa lanceolata Forssk. Thirteen natural, synthetic, semisynthetic, and microbially transformed analogs of 1 were tested for their in vitro inhibition of 5-lipoxygenase (5-LO) and cyclooxygenase-1 (COX-1). Maesanin was the most active 5-LO inhibitor. All other analogs were inactive or less active than the natural products as 5-LO inhibitors. None of the tested compounds was strongly active in the COX-1 inhibition assay.

Alkaloids from Haplophyllum tuberculatum.

Two new alkaloids, haplotubinone (3) and haplotubine (4), were isolated from the aerial parts of Haplophyllum tuberculatum together with the known lignan diphyllin. The structures of the new alkaloids were established by spectroscopic methods in conjunction with X-ray crystallographic analysis of 3. In addition, the amide N-(2-phenylethyl)-benzamide has been identified in this source for the first time.

Bioactive 12-oleanene triterpene and secotriterpene acids from Maytenus undata.

The aerial parts of Maytenus undata yielded four new 12-oleanene and 3,4-seco-12-oleanene triterpene acids, namely, 3-oxo-11alpha-methoxyolean-12-ene-30-oic acid (1), 3-oxo-11alpha-hydroxyolean-12-ene-30-oic acid (2), 3-oxo-olean-9(11), 12-diene-30-oic acid (3), and 3,4-seco-olean-4(23),12-diene-3, 29-dioic acid (20-epi-koetjapic acid) (5), together with the known 3, 11-dioxoolean-12-ene-30-oic acid (3-oxo-18beta-glycyrrhetinic acid) (4), koetjapic acid (6), and the 12-oleanene artifact 3-oxo-11alpha-ethoxyolean-12-ene-30-oic acid (7). Koetjapic acid (6) inhibited the growth of Staphylococcus aureus, methicillin-resistant S. aureus, and Pseudomonas aeruginosa, with an MIC range of 3.125-6.25 microg/mL. The new 3,4-secotriterpene acid 20-epi-koetjapic acid (5) potently inhibited rat neonatal brain microglia phorbol ester-stimulated thromboxane B(2) (IC(50) = 0.5 microM) and superoxide anion (IC(50) = 1.9 microM) generation.

2-Hydroxy-5-(ethanolamino)-3-(10'-Z-pentadecenyl)-1,4-benzoquinone, new microbial phase II metabolite of maesanin.

The use of microbial models for biotransformation of the natural benzoquinone, maesanin (1), resulted in the isolation of an ethanolamine conjugate (5) from the culture broth of Debaryomyces polymorphus ATCC 20280. Metabolite 5 was characterized as 2-hydroxy-5-(ethanolamino)-3-(10'-Z-pentadecenyl)-1,4-benzoq uinone. The production of 5 represents a new type of phase II conjugation reaction in microbial systems. The results of preliminary mammalian metabolism of 1 in rats were inconclusive.

Azaanthraquinone: an antimicrobial alkaloid from Mitracarpus scaber.

An ethanolic extract of the aerial parts of Mitracarpus scaber demonstrated good antimicrobial activity. Bioassay directed fractionation of this extract led to the isolation of benz[g]isoquinoline-5,10-dione (1) as an active component. Compound 1 showed significant in vitro inhibitory activity against the AIDS-related pathogens.

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.

Antifungal evaluation of pseudolaric acid B, a major constituent of Pseudolarix kaempferi.

Pseudolaric acid B [1] was isolated and identified as the main antifungal constituent of Pseudolarix kaempferi using bioassay-directed fractionation. Pseudolaric acid B was active against Trichophyton mentagrophytes, Torulopsis petrophilum, Microsporum gypseum, and Candida spp., while its methylated or hydrolyzed derivatives were not active against these same organisms. The minimum inhibitory concentrations and minimum fungicidal concentrations of pseudolaric acid B [1] against Candida and Torulopsis species were comparable with those of amphotericin B. The in vivo activity of pseudolaric acid B was evaluated in a murine model of disseminated candidiasis. Pseudolaric acid B [1] reduced the number of recovered colony-forming units significantly at different dosages. Infected mice treated intravenously with pseudolaric acid B [1] also had a longer survival time than those treated with vehicle alone.

Antimicrobial properties of alkaloids from Xanthorhiza simplicissima.

The organic extract of the whole plant Xanthorhiza simplicissima was found to exhibit good activity against the AIDS-related opportunistic pathogens Candida albicans, Cryptococcus neoformans, and Mycobacterium intracellularae. Bioassay-directed fractionation of the extract led to the isolation of the known alkaloid berberine as the major active component. A second alkaloid of the isohomoprotoberberine family, puntarenine, was isolated from this plant family for the first time. Puntarenine also showed marginal activity against the dermatophytic fungus Trichophyton mentagrophytes and the yeast Saccharomyces cerevisiae.

Antimicrobial compounds from Petalostemum purpureum.

EtOH extracts of Petalostemum purpureum demonstrated antimicrobial activity against bacteria and fungi. Bioassay-directed fractionation led to the isolation of petalostemumol [1] as the active constituent. Its structure was determined by a single crystal X-ray diffraction analysis. A minor component designated petalostemumol G [3] is believed to be an artifact of the isolation procedure. Its structure was confirmed by a single crystal X-ray analysis of its pentamethylether 2. A number of derivatives of 1 and 3, including the Me- and benzylethers and acetates, were prepared.

Preparation, characterization, and antiviral activity of microbial metabolites of stemodin.

Screening studies for microbial transformation products of stemodin [2] have identified a number of microbial metabolites. Scale-up fermentation with Rhizopus arrhizus ATCC 11145 and Streptomyces sp. NRRL 5691 have resulted in the production of five metabolites that have been characterized with the use of 2D nmr and X-ray techniques. These metabolites have been identified as 18-hydroxystemodin [6], 16,18-dihydroxystemodin [7], 8 beta-hydroxystemodin [8], 8 beta, 18-dihydroxystemodin [9], and 7 beta, 8 beta-dihydroxystemodin [10]. The antiviral activity and cytotoxicity of the isolated metabolites have been evaluated.

Use of microorganisms for the study of drug metabolism: an update.

The use of microorganisms as tools in the study of drug metabolism appears to be gaining popularity. The selected examples cited here provide additional evidence of the utility of these systems as alternative in vitro models for studying drug metabolism in humans. However, as was noted earlier, this model, nor any other in vitro model system could ever replace animals in biomedical research. However, it is apparent from the numerous examples cited here and in the previous review of this area that microorganisms are a reliable, reproducible alternative to small animals as predictive models in drug metabolism studies. The continuing development of techniques that reduce the use of animals in research is encouraged and this procedure appears to be gaining more widespread acceptance for such use.

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.

Antifungal activity of Trillium grandiflorum constituents.

EtOH extracts of the rhizomes and aboveground portion of Trillium grandiflorum showed significant antifungal activity. Bioassay directed fractionation has led to the identification of the active components as the saponin glycosides 1 and 3.

In vivo efficacy of antifungal oxoaporphine alkaloids in experimental disseminated candidiasis.

The efficacy of three antifungal oxoaporphine alkaloids, liriodenine, liriodenine methiodide, and oxoglaucine methiodide, was determined in a mouse model of disseminated candidiasis. Mice infected with a lethal dose of Candida albicans NIH B311 were administered varying doses of each drug intraperitoneally or intravenously 7 hr postinfection. Reductions in the number of colony-forming units (CFU) recovered per milligram of kidney tissue were observed in drug-treated animals compared to vehicle-treated control mice. Significance was determined by the Wilcoxon nonparametric rank sum test. Intravenous administration of both liriodenine and liriodenine methiodide resulted in a significant reduction in the number of recovered CFU, while there was no significant response to treatment with oxoglaucine methiodide.

Antimicrobial activities of constituents of Uvaria chamae.

The antimicrobial activities of a number of cytotoxic C-benzylated flavonoids from Uvaria chamae have been determined. The minimum inhibitory concentration values of these flavonoids and certain of their derivatives against Straphylococcus aureus, Bacillus subtilis, and Mycobacterium smegmatis compare favorably with those of streptomycin sulfate.