Mannopeptimycins alpha, beta, gamma, delta, and epsilon are new cyclic glycopeptide antibiotics produced by Streptomyces hygroscopicus LL-AC98. Mannopeptimycins gamma, delta, and epsilon, which have an isovaleryl substitution at various positions on the terminal mannose of the disaccharide moiety, demonstrated moderate to good antibacterial activities. Mannopeptimycin epsilon was the most active component against methicillin-resistant staphylococci and vancomycin-resistant enterococci (MICs, 2 to 4 micro g/ml for staphylococci and streptococci and 4 to 32 micro g/ml for enterococci), while mannopeptimycins gamma and delta were two- to fourfold less active. Mannopeptimycins alpha and beta, which lack the isovaleryl substitution and the disaccharide moiety, respectively, had poor antibacterial activities. The in vivo efficacies of the mannopeptimycins in Staphylococcus aureus mouse protection studies paralleled their in vitro activities. The median effective doses of mannopeptimycins gamma, delta, and epsilon were 3.8, 2.6, and 0.59 mg/kg of body weight, respectively. The mannopeptimycins were inactive against cell wall-deficient S. aureus and caused spheroplasting of Escherichia coli imp similar to that observed with penicillin G in an osmotically protective medium. Mannopeptimycin delta rapidly inhibited [(3)H]N-acetylglucosamine incorporation into peptidoglycan in Bacillus subtilis and had no effect on DNA, RNA, or protein biosynthesis. On the basis of the observations presented above, an effect on cell wall biosynthesis was suggested as the primary mode of action for mannopeptimycin delta. The mannopeptimycins were inactive against Candida albicans, did not initiate hemolysis of human erythrocytes, and did not promote potassium ion leakage from E. coli imp, suggesting a lack of membrane damage to prokaryotic or eukaryotic cells.
Fermentation extracts of culture CR11 5, an unknown plant endophyte originally isolated from Costa Rica, were found to be active against antibiotic-resistant bacteria. The metabolite responsible for activity was identified as a novel diterpenoid antibiotic guanacastepene (mol. wt. 374.47 and mol. formula C22H30O5). Mechanistic studies done in an E. coli imp strain suggested membranedamage as the primary modeof bactericidal action. This compoundalso lysed human RBCsand caused leakage of intracellular potassium from E. coli imp. Screening of unusual fungi from various ecological niches around the world has been productive in yielding new bioactive metabolitesl~7\ During our screening of fungal fermentation extracts, an unidentified terrestrial fungus CR1 15 was found to exhibit antibacterial activity against methicillin-resistant Staphylococcus aureus and
Four new indolosesquiterpenes, lecanindoles A-D (1-4), were isolated from fermentations of the terrestrial fungus Verticillium lecanii 6144. The structures of compounds 1-4 were elucidated from analysis of spectroscopic data. Compound 2 was reduced to give 4 and its isomer 5. Compound 4 was found to be a potent and selective progesterone receptor agonist with an EC50 of 1.1 +/- 0.4 nM in a cell-based luciferase reporter assay.
The purpose of this study was to evaluate the effectiveness of full three‐dimensional (3D) gamma algorithm for spot scanning proton fields, also referred to as pencil beam scanning (PBS) fields. The difference between the full 3D gamma algorithm and a simplified two‐dimensional (2D) version was presented. Both 3D and 2D gamma algorithms are used for dose evaluations of clinical proton PBS fields. The 3D gamma algorithm was implemented in an in‐house software program without resorting to 2D interpolations perpendicular to the proton beams at the depths of measurement. Comparison between calculated and measured dose points was carried out directly using Euclidian distance in 3D space and the dose difference as a fourth dimension. Note that this 3D algorithm faithfully implemented the original concept proposed by Low et al. (1998) who described gamma criterion using 3D Euclidian distance and dose difference. Patient‐specific proton PBS plans are separated into two categories, depending on their optimization method: single‐field optimization (SFO) or multifield optimized (MFO). A total of 195 measurements were performed for 58 SFO proton fields. A MFO proton plan with four fields was also calculated and measured, although not used for treatment. Typically three different depths were selected from each field for measurements. Each measurement was analyzed by both 3D and 2D gamma algorithms. The resultant 3D and 2D gamma passing rates are then compared and analyzed. Comparison between 3D and 2D gamma passing rates of SFO fields showed that 3D algorithm does show higher passing rates than its 2D counterpart toward the distal end, while little difference is observed at depths away from the distal end. Similar phenomenon in the lateral penumbra was well documented in photon radiation therapy, and in fact brought about the concept of gamma criterion. Although 2D gamma algorithm has been shown to suffice in addressing dose comparisons in lateral penumbra for photon intensity‐modulation radiation therapy (IMRT) plans, results here showed that a full 3D algorithm is required for proton dose comparisons due to the existence of Bragg peaks and distal penumbra. A MFO proton plan with four fields was also measured and analyzed. Sharp dose gradients exist in MFO proton fields, both in the middle of the modulation and toward the most distal layers. Decreased 2D gamma passing rates at locations of high dose gradient are again observed as in the SFO fields. Results confirmed that a full 3D algorithm for gamma criterion is needed for proton PBS plan's dose comparisons. The 3D gamma algorithm is implemented by an in‐house software program. Patient‐specific proton PBS plans are measured and analyzed using both 3D and 2D gamma algorithms. For measurements performed at depths with large dose gradients along the beam direction, gamma comparison passing rates using 2D algorithm is lower than those obtained with the full 3D algorithm.PACS number: 87.53.Bn, 87.53.Jw, 87.55.de, 87.55.kd, 87.55.ne, 87.55.Qr
Echinosporamicin (1), a novel antibiotic containing an aromatic polycyclic system and a piperazinone moiety, was isolated from the fermentation broth of a new strain of Micromonospora echinospora subspecies echinospora, LL‐P175. The structure of this compound was determined by spectroscopic analysis by using variable‐temperature NMR techniques. Compound 1 exhibited potent activity against methicillin‐resistant Staphylococci and vancomycin‐resistant Enterococci strains. The methyl, ethyl, and benzyl esters showed improved antibacterial activity against Streptococci.
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