Phomol (1), a novel antibiotic, was isolated from fermentations of a Phomopsis species in the course of a screening of endophytic fungi from the medicinal plant Erythrina crista-galli. For this Argentinean leguminosa antiinflammatory and neuroleptic activities have been described. The compound exhibits antifungal, antibacterial and weak cytotoxic acticity. The antiinflammatory activity was tested in different reporter gene assays (TNF-α, STAT1/STAT2 and NF-κB) and in an ear edema model in mice. In the reporter gene assays 1 exhibited no activity, whereas 1 showed interesting antiinflammatory activity in the mouse ear assay. The compound is a polyketide lactone and its structure was elucidated by spectroscopic methods.
From a fungal strain FKI-0929, two compounds designated epohelmins A and B, were isolated as new natural products with inhibitory activity against recombinant human lanosterol synthase. The crude extract from the whole broth of this strain was fractionated by silica gel column chromatography and HPLC to afford two isolated inhibitors. Detailed spectroscopic analyses led to the identification of their structures. They are diastereomers of 4, 5-epoxy-2-(4'-oxoundec-(5'E)-enyl)-heptamethylenamines, and their relative stereochemical configurations were determined as (2R, 4R, 5R) or (2S, 4S, 5S) for epohelmin A, and (2R, 4S, 5R) or (2S, 4R, 5S) for epohelmin B, respectively. These compounds inhibited recombinant human lanosterol synthase with IC50 values of 10 and 6.0μM, respectively.
A novel antifungal antibiotic, YM-193221, was found in the culture broth of a fungus, Pseudallescheria ellipsoidea. The structure of the antibiotic was determined through several spectroscopic experiments as 2-dimethylamino-1-(4-hydroxyphenyl)-8, 10-dimethyl-6-dodecene-3-one. YM-193221 exhibited potent antifungal activity against Candida albicans and also inhibited mannan synthesis in the yeast cell wall.
In the screening of searching for new antifungal agents, a new nonaride compound, dihydroepiheveadride (1), was isolated from unidentified fungus IFM 52672 as the most potent antifungal principle from this organism. The structure of 1 was established on the basis of spectroscopic and chemical investigation, as well as detailed comparison of the spectroscopic and physico-chemical data of the oxidized derivative (3) from 1 with those of heveadride (2). Compound 1 showed strong antifungal activity against various filamentous fungi including human pathogens Aspergillus fumigatus, Penicillium marneffei and Trichophyton spp. It also showed the growth inhibition activity against certain human pathogenic yeasts such as Trichosporon species, while it had weak or no antifungal activity against Candida spp. and Cryptococcus neoformans, and no antibacterial activity against Bacillus subtilis nor against Escherichia coli. The antifungal potencies of compounds 2 and 3 were found to be weaker than that of 1.
The API-MS spectra of 6-deoxyerythronolide B (6-dEB) and a number of its analogs have been studied to gain information into the fragmentation patterns of 6-deoxyerythronolides under atmospheric pressure ionization conditions. The API-MS spectrum of 6-dEB shows five major families of fragments. The spectra of a series of desmethyl-6-dEBs allow assignment of these fragment families to structural subunits as well as provide information regarding the fragmentation mechanisms. The spectrum of [9-18O]-6-dEB is consistent with loss of the ketone oxygen during the first dehydration, and the spectra of other oxygen-modified analogs implicate the non-obligate formation of a 5, 9-hemiacetal in the initial stages of fragmentation. These results taken together are used to propose a model for the fragmentation of 6-dEB and its analogs under API conditions.
The antibiotic thiazole compound siomycin, which we have found from the culture broth of Actinomycetes (strain No. 806097) in search of antibody production inhibitor, showed the in vitro immunosuppressive property against B-cells stimulated with T-cell independent antigen DNP-LPS (dinitrophenyl-lipopolysaccharide) while it also showed inhibitory effect against T-cell proliferation. Its inhibitory mechanism was considered to be different from that of FK506, the representative of T-cell immunosuppressant. Moreover, siomycin showed inhibitory effect in both T-cell dependent and independent murine antibody production models and decreased the severity in murine collagen arthritis model. Therefore, siomycin is a unique immunosuppressant which has potential for the treatment of some antibody-mediated diseases.