-Schistosomal activity and ADMET properties of 1,2,5-oxadiazinane-containing compound synthesized by visible-light photoredox catalysis.

The incorporation of saturated nitrogen-containing heterocycle 1,2,5-oxadiazinane into small molecules represents a compelling avenue in drug discovery due to its unexplored behavior within biological systems and incomplete protocols for synthesis. In this study, we present 1,2,5-oxadiazinane, an innovative heterocyclic bioisostere of piperizin-2-one and novel chemotype of the -schistosomal drug praziquantel (PZQ), which has been the only clinical drug available for three decades. PZQ is associated with significant drawbacks, including poor solubility, a bitter taste, and low metabolic stability.

Development of a nitrogen-bound hydrophobic auxiliary: application to solid/hydrophobic-tag relay synthesis of calpinactam.

In the last couple of decades, technologies and strategies for peptide synthesis have advanced rapidly. Although solid-phase peptide synthesis (SPPS) and liquid-phase peptide synthesis (LPPS) have contributed significantly to the development of the field, there have been remaining challenges for C-terminal modifications of peptide compounds in SPPS and LPPS. Orthogonal to the current standard approach that relies on installation of a carrier molecule at the C-terminus of amino acids, we developed a new hydrophobic-tag carbonate reagent which facilitated robust preparation of nitrogen-tag-supported peptide compounds.

Polyketide glycosides phialotides A to H, new potentiators of amphotericin B activity, produced by Pseudophialophora sp. BF-0158.

Eight new potentiators of antifungal amphotericin B (AmB) activity, phialotides A to H, were isolated from the fermentation broths of the rare fungus Pseudophialophora sp. BF-0158. The structures of phialotides were elucidated by spectroscopic analyses, including NMR and MS, and degradation studies.

Clinical Pharmacy Education in Japan: Using Simulated Patients in Laboratory-Based Communication-Skills Training before Clinical Practice.

The Japanese pharmaceutical curriculum was extended from four to six years in 2006. Students now receive practical communication-skills training in their fourth year, before progressing to train in hospital and community pharmacies in their fifth year. Kitasato University School of Pharmacy, Tokyo, had established a program to meet these aims before the 2006 guidance.

Inhibition of adenosine deaminase (ADA)-mediated metabolism of cordycepin by natural substances.

Cordycepin, which is an analogue of a nucleoside adenosine, exhibits a wide variety of pharmacological activities including anticancer effects. In this study, ADA1- and ADA2-expressing HEK293 cells were established to determine the major ADA isoform responsible for the deamination of cordycepin. While the metabolic rate of cordycepin deamination was similar between ADA2-expressing and Mock cells, extensive metabolism of cordycepin was observed in the ADA1-expressing cells with K m and V max values of 54.

Extensive protein interactions involving cytochrome P450 3A4: a possible contributor to the formation of a metabolosome.

Cytochrome P450 (CYP) 3A4 is a membrane protein that catalyzes hydroxylation of endogenous and exogenous substrates. Protein-protein interaction is a crucial factor that regulates the function of enzymes. However, protein-protein interactions involving human CYPs have not been fully understood.

Expression pattern of human ATP-binding cassette transporters in skin.

ATP-binding cassette (ABC) transporters transport a variety of substrates across cellular membranes coupled with hydrolysis of ATP. Currently 49 ABC transporters consisting of seven subfamilies, ABCA, ABCB, ABCC, ABCD, ABCE, ABCF, and ABCG, have been identified in humans and they are extensively expressed in various tissues. Skin can develop a number of drug-induced toxicities' such as Stevens-Johnson syndrome and psoriasis.

Glucuronidation of drugs in humanized UDP-glucuronosyltransferase 1 mice: Similarity with glucuronidation in human liver microsomes.

Uridine 5'-diphosphate-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that catalyze glucuronidation of various endogenous and exogenous substrates. Among 19 functional human UGTs, UGT1A family enzymes largely contribute to the metabolism of clinically used drugs. While the UGT1A locus is conserved in mammals such as humans, mice, and rats, species differences in drug glucuronidation have been reported.

[Significance of the term "huku-yaku" (taking medicines)].

The term "Huku or Fu" in "Huku-yaku or Fu-yao", which means taking medicines, does not mean " to wear" , but means "to obey certain rituals or duties." Therefore "Huku-yaku (Fu-yao)" means " to obey the nature of a drug." From the viewpoint of "ShenXian" thought, the term used when referring to taking medicine depends on whether the purpose is to cure diseases or strengthen pneuma.

New beauvericins, potentiators of antifungal miconazole activity, Produced by Beauveria sp. FKI-1366. II. Structure elucidation.

The structures of beauvericins D, E and F, novel potentiators of miconazole activity against Candida albicans produced by Beauveria sp. FKI 1366, were elucidated by various spectroscopic analyses including UV, NMR, and MS and degradation experiments. They have the common skeleton of the 18-membered cyclodepsipeptides.