A-53930A and B, novel N-type Ca2+ channel blockers.

A-53930A, B and C, which inhibit N-type Ca2+ channels, were isolated from the culture broth of Streptomyces vinaceusdrappus SANK 62394. A-53930A and B were new compounds which contained a carbamoyl group on the 6-hydroxyl group of the D-gulosamine part of streptothricin. A-53930C was identical to streptothricin B. A-53930A, B and C inhibited [125I]omega-conotoxin MVIIA binding to N-type Ca2+ channels (IC50= 0.17, 0.091 and 0.071 microM), but did not inhibit [3H]PN200-110 binding to L-type Ca2+ channels (IC50 > 50 microM). These compounds also inhibited [3H]norepinephrine release from chick cerebral cortex synaptosomes (IC50=91.0, 20.6 and 39.5 microM), indicating these compounds selectively block N-type Ca2+ channels which are important for neurotransmitter release. It was also revealed that although A-53930C had antimicrobial activity against gram-negative and -positive bacteria and fungi, A-53930A and B showed weak activity only against gram-negative bacteria.

A-72363 A-1, A-2 and C, novel heparanase inhibitors from Streptomyces nobilis SANK 60192. I. Taxonomy of producing organism, fermentation, isolation and structure elucidation.

Novel heparanse inhibitors, A72363 A-1, A-2, and C, were isolated from the culture filtrate of Streptomyces nobilis SANK 60192 by column chromatography on various resinous adsorbents, followed by preparative anion exchange HPLC. Spectroscopic studies revealed that they are diastereomers of siastatin B, a neuraminidase inhibitor.

Novel microbial metabolites of the phoslactomycins family induce production of colony-stimulating factors by bone marrow stromal cells. I. Taxonomy, fermentation and biological properties.

Three metabolites were isolated from the culture broth of an actinomycete strain identified as Streptomyces platensis SANK 60191, that induce the production of colony-stimulating factors (CSFs) by stromal cell line KM-102 at ED50 concentrations from 40 to 200 ng/ml. The compounds induced quantities of granulocyte CSF (G-CSF) and granulocyte-macrophage CSF (GM-CSF) comparable to those induced by interleukin-1, a strong CSF inducer. These metabolites were called leustroducsins (A, B and C) and were later found to be structurally related to phoslactomycins. This is the first report of CSF inducing activity by members of the phoslactomycin class.

Mureidomycins E and F, minor components of mureidomycins.

Mureidomycins (MRDs) E and F were isolated from a culture filtrate of Streptomyces flavidovirens SANK 60486 which produces MRDs A approximately D. They possessed the same molecular formulae, C39H48N8O12S and very similar UV, IR and NMR spectra, but differed clearly from each other in HPLC profile. From the hydrolysates of MRDs E and F, 8-hydroxy-1,2,3,4-tetrahydro-3-isoquinoline carboxylic acid and 6-hydroxy-1,2,3,4-tetrahydro-3-isoquinoline carboxylic acid were detected, respectively, which were not detected from those of MRDs A approximately D. They showed strong anti-pseudomonal activity but less active than MRD A. MRDs E and F were synthesized from MRD A and formaldehyde through Pictet-Spengler reaction.

Galacardins A and B, new glycopeptide antibiotics.

A strain of actinomycetes identified as Saccharothrix sp. SANK 64289 was found to produce new antibiotics, galacardins A and B. Their physico-chemical properties showed that they were new members of glycopeptide antibiotics. They were structurally related to beta-avoparcin but differed from it only in sugar composition. Though beta-avoparcin does not contain galactose, galacardins A and B did contain two and one moles of galactose, respectively. They showed strong antimicrobial activity against Gram-positive bacteria and also showed excellent in vivo protective activity against Staphylococcus aureus infection in mice.

Mureidomycins A-D, novel peptidylnucleoside antibiotics with spheroplast forming activity. I. Taxonomy, fermentation, isolation and physico-chemical properties.

A strain of actinomycetes identified as Streptomyces flavidovirens produced new antibiotics, mureidomycins (MRD's) A approximately D, specifically active against Pseudomonas aeruginosa. They were isolated from the culture filtrate by successive column chromatographies such as Amberlite XAD-2 and CG-50, Whatman DE-52 and Toyopearl HW-40. They were amphoteric white powders and soluble in methanol and water. Their molecular weights and molecular formulae in parentheses were 840 (C38H48N8O12S), 842 (C38H50N12S), 897 (C40H51N9O13S) and 899 (C40H53N9O13S), respectively. m-Tyrosine and two unknown substances were detected by amino acid analyses as their common constituents. MRD's A and C contained uracil but MRD's B and D dihydrouracil instead of uracil.

[Effect of loading time on the Vickers hardness number of dental gold alloys].

The Vickers hardness number (VHN) of pure metals (tin, aluminum, copper and gold) and dental gold alloys was measured using an automatically indenting and reading Vickers hardness tester (AKASHI.AUTOVICK) under a load of 1,000 gf with different loading times of 5 to 55 seconds. The samples of pure metals were cold rolled and softened by heating above recrystallization temperatures. The samples of ADAS No. 5 gold casting alloys were cold rolled, and then subjected to a softening heat treatment by water quenching (Types I, II, III and IV) or a hardening heat treatment by 450-250 degrees C/30 min oven cooling (Types III and IV). The results showed that there were no statistically significant differences between the measured values of VHN of a sample with different loading times as for the metals studied except pure tin which had a VHN of 5-6. The measured values of VHN by AUTOVICK were affected by the brightness of a light source for measurement, and they increased by 1.1 approximately as the voltage of the light source increased by 0.1 V. This was considered to be due to the protuberance caused by plastic flow of metals or slip lines on the surface around the indentation.

Chloropolysporins A, B and C, novel glycopeptide antibiotics from Faenia interjecta sp. nov. II. Fermentation, isolation and physico-chemical characterization.

New antibiotics, chloropolysporins A, B and C, were found in the culture broth of an actinomycete identified as Faenia interjecta sp. nov. They were isolated from the culture filtrate by column chromatography on various resinous adsorbents, followed by preparative reverse phase HPLC. Chloropolysporins A, B and C possessed all the same new aglycone composed of actinoidic acid, 3-chloro-4-hydroxyphenylglycine, N-methyl-p-hydroxyphenylglycine and vancomycinic acid. From elementary analyses and mass spectroscopic measurements, the molecular formulae of chloropolysporins A, B and C appear to be C89H99O39N8Cl3 (MW 2,008), C83H89O34N8Cl3 (MW 1,846) and C77H79O30N8Cl3 (MW 1,700), respectively. Their physico-chemical characterizations including molecular formulae revealed that chloropolysporins A, B and C were new members of glycopeptide antibiotics.