No abstract

The abuse of antibacterial drugs imposes a selection pressure on bacteria that has driven the evolution of multidrug resistance in many pathogens. Our efforts to discover novel classes of antibiotics to combat these pathogens resulted in the discovery of amycolamicin (AMM). The absolute structure of AMM was determined by NMR spectroscopy, X-ray analysis, chemical degradation, and modification of its functional groups. AMM consists of trans-decalin, tetramic acid, two unusual sugars (amycolose and amykitanose), and dichloropyrrole carboxylic acid. The pyranose ring named as amykitanose undergoes anomerization in methanol. AMM is a potent and broad-spectrum antibiotic against Gram-positive pathogenic bacteria by inhibiting DNA gyrase and bacterial topoisomerase IV. The target of AMM has been proved to be the DNA gyrase B subunit and its binding mode to DNA gyrase is different from those of novobiocin and coumermycin, the known DNA gyrase inhibitors.

A fluorine-doped tin oxide-coated glass electrode modified with a bilayer film of underlying α-Co­(OH)2 and overlying Mg-intercalated and Co-doped δ-type (layered) MnO2 (Mg|Co-MnO2) preferentially yielded oxygen with a Faradaic efficiency as high as 79% in the presence of chloride ions at high concentration (0.5 M). This noble metal-free electrode was fabricated by cathodic electrolysis of aqueous Co­(NO3)2 followed by anodic electrolysis of a mixture of Mn2+, Co2+, and cetyltrimethylammonium (CTA+) ions in water. The CTA+ ions accommodated in the interlayer spaces of Co-doped δ-MnO2 were replaced with Mg2+ by ion exchange. The upper Mg|Co-MnO2 could effectively block the permeation of Cl– ions and allow only H2O and O2, while the under α-Co­(OH)2 acted as an oxidation catalyst for the H2O penetrated through the upper coating. Thus, the oxygen evolution reaction (OER) was preferred to the chlorine evolution reaction (CER). In artificial seawater (pH 8.3), the blocking effect against Cl– decreased because of ion exchange of the intercalated Mg2+ ions with Na+ in solution, but the OER efficiency still remained at 57%, much higher than that (28%) without the upper Mg|Co-MnO2. This demonstrates that the interlayer spaces between MnO2 layers acted as pathways for H2O molecules to reach the active sites of the underlying Co­(OH)2. Density functional theory (DFT) calculations revealed that the most stable structure of hydrated Mg2+ ion, in which a part of coordinated H2O molecules is hydrolyzed, has less affinity toward Cl– ion than that of hydrated Na+ ion.

Even though the oxygen evolution reaction (OER) is thermodynamically much more favored than the chlorine evolution reaction (CER), the former is much more sluggish. Thus, electrolysis of solutions containing a high concentration of chlorides yields preferentially chlorine. In this study, a thin film consisting of oxygen-deficient and disordered manganese oxide nanolayers on a fluorine-doped tin oxide (FTO) electrode exhibited a high selectivity for OER over CER in 0.5 M NaCl solution. The catalyst was fabricated by electrodeposition of layered manganese dioxide intercalated with Na+ ions (Na|MnO2) followed by heat treatment above 300 °C in air. X-ray photoelectron spectroscopy revealed that, at 200 °C, oxygen vacancies started to form, accompanied by a decrease in the valence state of Mn in the oxide. The X-ray diffraction and absorption fine structure data revealed that, above 300 °C, the multilayered structure of Na|MnO2 that had been constructed during electrodeposition was disordered to yield “oxygen-deficient” MnO x nanolayers, which could lead to an increase in catalytic activity and selectivity for OER. The Na|MnO x film heat-treated at 400 °C showed a Faradaic efficiency as high as 87% in galvanostatic electrolysis at 10 mA cm–2. The Mg2+-intercalated MnO2 electrodeposited similarly did not lose its multilayered structure and did not show a decrease in the Mn valence state during heat treatment, and its activity and selectivity for OER were much inferior to those obtained with Na+.

Because stromal cells can regulate the growth and metastasis of tumor cells, a compound that modulates the interaction between the stromal cells and the tumor cells can control the tumor progression. In the course of our screening for such a compound, we have isolated a new compound, intervenolin, from the culture broth of Nocardia sp. ML96-86F2. Intervenolin inhibits the growth of human gastric and colorectal cancer cell lines in the coculture with the respective organ-derived stromal cells more strongly than that of the cancer cells cultured alone. Intervenolin shows antitumor effect against a xenograft model of human colorectal cancer cells in vivo. Furthermore, intervenolin exerts selective anti-Helicobacter pylori effect.