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In vivo characterization of A-192411: a novel fungicidal lipopeptide (II).

The ability of the novel antifungal cyclic hexalipopetide A-192411 to treat fungal infections in rodents is presented. Efficacy was demonstrated against Candida albicans as both prolonged survival of systemically infected mice and clearance of viable yeasts from kidneys. The efficacy of A-192411, administered intraperitoneally, was equivalent to amphotercin B at a 4-fold lower dose by weight in the systemic candidiasis models in mice, while the efficacy of A-192441 administered intravenously was equivalent to amphotercin B by weight in the Candida pyelonephritis model in rats. A-192411 also slightly prolonged the survival of immunocompromised mice infected systemically with Aspergillus fumigatus.

Amphotericin B↗

Fungicidal properties of meso-arylglycosylporphyrins: influence of sugar substituents on photoinduced damage in the yeast Saccharomyces cerevisiae.

A series of neutral meso-arylglycosylporphyrins has been tested in order to evaluate their potency as antifungal agents against the yeast Saccharomyces cerevisiae. Photodynamic activity of these molecules results in intracellular damage as evidenced by the loss of clonogenicity and DNA fragmentation. The ability of these photosensitizers to permeate yeast cells is determined by microspectrofluorimetry and is correlated with their antifungal potency. Amphiphilic porphyrin derivatives are shown to exhibit the more pronounced photoactivity.

Antifungal Agents↗

Detection and characterization of DNA adducts formed from metabolites of the fungicide ortho-phenylphenol.

The significance of DNA adduction in ortho-phenylphenol-induced carcinogenesis remains unclear. Establishing adduct structures may contribute to resolving this issue. The chemical structures of the DNA adduction products resulting from the in vitro reaction of phenylbenzoquinone, the putative ultimate carcinogenic metabolite of the fungicide/disinfectant ortho-phenylphenol, are reported here. Three isomeric adducts that resulted from reaction of deoxyguanosine were characterized by UV, LC-ESI-MS, and MS/MS, and 1D and 2D COSY-NMR spectroscopy. The proposed mechanism of product formation is nucleophilic attack by the deoxyguanosine exocyclic amine nitrogen on an electrophilic quinone carbon, followed by stabilization through enolization. Another nucleophilic attack forms a five-membered ring, which aromatizes by dehydration to form the final product. Adducts were also characterized from deoxyadenosine and deoxycytidine, although conversions were at least 10 times lower. Structures are also proposed for these products. Cell culture studies confirmed that HepG2 cells incubated with phenylbenzoquinone at concentrations associated with cytotoxicity form the same DNA adducts.

Benzoquinones↗

Determination of the antibiotic fungicide validamycin A in formulated products by micellar electrokinetic chromatography.

A micellar electrokinetic capillary chromatographic method (MEKC) was used to determine validamycin A content in commercial products. The results indicated that this method was capable of analyzing the validamycin A content in formulated products with an instrument detection limit of 0.94 microg/mL and a method detection limit of 1. 70 microg/mL. Relative standard deviation (RSD) values of MEKC determination of validamycin A in formulated products ranged from 0. 61 to 2.09%. Recoveries of validamycin A in formulated products were in the region of 99.5-105.1%. All commercial products collected from markets contained validamycin A. The high percentage of recovery, the low detection limit, and the low RSD values confirmed that the MEKC technique is a senstivie and selective method.

Anti-Bacterial Agents↗