Darkness-induced factor affecting basidiocarp maturation in Coprinus macrorhizus

Graftings were made between young basidiocarps of Coprinus macrorhizusgrown under different light programs. Results showed that adiffusible factor(s) affecting basidiocarp maturation was inducedby the darkness of phase 3. (Received July 3, 1979; )     

Microbial and enzymatic processes for the production of pharmacologically important nucleosides

S-Adenosylmethionine, S-adenosylhomocysteine and related nucleosides have recently attracted great interest as key regulatory compounds in many biological transmethylation systems. Although these nucleosides in the pharmacological and chemotherapeutic fields have great potential, no process for their practical production has been developed yet. One of the problems is in the elucidation of the complex relationships between these nucleosides and the control mechanisms of biological transmethylations. This review shows, however, that some of these useful compounds can now be very easily produced by microbial or enzymatic processes.     

Regiospecific hydrolysis of dinitrile compounds by nitrilase fromRhodococcus rhodochrous J1

Summary Nitrilase fromRhodococcus rhodochrous J1 catalyses the hydrolysis of nitriles to acids without the formation of amides. TheRhodococcus nitrilase exhibited regiospecificity for dicyanobenzenes. Three- and 4-cyanobenzoic acids were synthesized from isophthalonitrile and terephthalonitrile, respectively, with conversion ratios of more than 90% using theRhodococcus nitrilase.     

Excitation of indole analogs by phagocytosing leukocytes

The system suspended with phagocytosing leukocytes and related system produce weak light which could be greatly amplified by indole analogs with plain fatty acids at 3 position. Main emitting species in indole-3-acetic acid or indole-3-propionic acid-sensitized system was analyzed spectrometrically in the dark and ascribed to the transition of an excited indole compound in triplet state to its ground state. Such an excited species would be generated by the oxidative way of the indole analogs but not through the dioxetane structure of 2 and 3 positions on indole ring.     

Abundance estimation of riverine macrophyte Egeria densa using environmental DNA: effects of sampling season and location

Invasive macrophytes can have a variety of effects on aquatic ecosystems. The early detection and abundance estimation of an invasive species is important to effectively control it and minimize the ecosystem impacts. It is imperative to develop more efficient sampling methods for the abundance quantification of aquatic plants in large riverine systems. We examined (1) relationships between the environmental DNA (eDNA) concentrations of the invasive macrophyte, Egeria densa, and the upstream coverage area on the multiple life-history stages (dormant, growing, and senescence seasons) in a large riverine system in Japan and (2) if the relationships between the eDNA concentrations and coverage area could vary with the lateral sampling locations (left bank, middle, and right bank). The eDNA concentrations had significant positive relationships with the upstream coverage area of E. densa at multiple spatial scales for the dormant and senescence seasons. These results suggest that the eDNA analysis could be useful to quantify the relative abundance of this aquatic macrophyte in the riverine system; however, the selection of the eDNA sampling season could be important to accurately estimate abundance. Our results also showed that the eDNA concentrations of E. densa did not significantly differ from the lateral sampling location, suggesting that the eDNA samples could reflect the relative abundance of E. densa upstream of the study sites regardless of the lateral sampling location.

     

Development of an anti-hepatitis B virus (HBV) agent through the structure-activity relationship of the interferon-like small compound CDM-3008

Hepatitis B, a viral infectious disease caused by hepatitis B virus (HBV), is a life-threatening disease that leads liver cirrhosis and liver cancer. Because the current treatments for HBV, such as an interferon (IFN) formulation or nucleoside/nucleotide analogues, are not sufficient, the development of a more effective agent for HBV is urgent required.CDM-3008 (1, 2-(2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridin-8-yl)-1,3,4-oxadiazole) (RO8191)) is a small molecule with an imidazo[1,2-a][1,8]naphthyridine scaffold that shows anti-HCV activity with an IFN-like effect. Here, we report that 1 was also effective for HBV, although the solubility and metabolic stability were insufficient for clinical use. Through the structure-activity relationship (SAR), we discovered that CDM-3032 (11, N-(piperidine-4-yl)-2,4-bis(trifluoromethyl)imidazo[1,2-a][1,8]naphthyridine-8-carboxamide hydrochloride) was more soluble than 1 (>30?mg/mL for 11 versus 0.92?mg/mL for 1). In addition, the half-life period of 11 was dramatically improved in both mouse and human hepatic microsomes (T1/2, >120?min versus 58.2?min in mouse, and >120?min versus 34.1?min in human, for 11 and 1, respectively).     

Discovery of NR2B-selective antagonists via scaffold hopping and pharmacokinetic profile optimization

Selective N-methyl-d-aspartate receptor subunit 2B (NR2B) antagonists show potential as analgesic drugs, and do not cause side effects associated with non-selective N-methyl-d-aspartate (NMDA) antagonists. Using a scaffold-hopping approach, we previously identified isoxazole derivative 4 as a potent selective NR2B antagonist. In this study, further scaffold hopping of isoxazole derivative 4 and optimization of its pharmacokinetic profile led to the discovery of the orally bioavailable compound 6v. In a rat study of analgesia, 6v demonstrated analgesic effects against neuropathic pain.