Design and synthesis of novel triazine derivatives as antimalarial agents.

In a previous study, we reported that nilotinib, a BCR-ABL tyrosine kinase inhibitor, possesses moderate antimalarial activity against PfK1 and PfFCR3. As a part of our efforts to develop novel antimalarial agents, a series of novel triazine analogs was identified as potent antimalarial agents via structure modification of nilotinib. Compound 15a showed strong antimalarial activities against PfK1 and PfFCR3 with IC values of 0.

Novel Tetrapeptides, Tengupeptins A and B, Produced by Lecanicillium aphanocladii FKI-9593 Fungal Strain.

The discovery of novel natural products through the exploration of distinct microorganisms is crucial for advancing drug discovery research. In this study, we focus on a unique environmental resource, microbial masses known as "Tengu-no-Mugimeshi." From the culture broth of Lecanicillium aphanocladii FKI-9593, isolated from Tengu-no-Mugimeshi collected at Mount Kurohime, Nagano Prefecture, Japan, we report the isolation of two novel tetrapeptides, tengupeptins A (1) and B (2), as well as the known compound oosporein.

Characterization of integrative and conjugative elements carrying erm(B) and tet(O) resistance determinants in streptococcus uberis isolates from bovine milk in Chiba prefecture, Japan: CompArative GEne cluster analysis toolbox with ICEfinder.

Objective: We aimed to characterize integrative and conjugative elements (ICEs) in antimicrobial resistant Streptococcs uberis isolates from bovine milk in Chiba, Japan, based on whole-genome sequence (WGS) data.

Results: Of the 101 isolates, we found the 36 isolates harboring erm(B)-tet(O), showing resistance to macrolides-lincosamides-tetracyclines. The 22 isolates were randomly selected and subject to WGS determination.

Palladium-Catalyzed Reductive and Redox-Neutral Cyclization Approach to the Southern Core of Avermectins.

The avermectins make up a biologically relevant class of complex natural products that continue to inspire the development of new strategies in chemical synthesis. Herein, we disclose a concise synthesis of the southern core of avermectin aglycon. The key hydrobenzofuran was forged by either reductive cyclization or cycloisomerization, both using a cationic palladium precatalyst.

Unusual G9P[4] Rotavirus Emerged After the Dynamic Changes in Rotavirus Genotypes From Equine-Like G3 to Typical Human G1/G3 in Indonesia.

Inter-genogroup reassortment of Rotavirus A (RVA) strains has highlighted the spread of unusual RVA strains worldwide. We previously reported the equine-like G3 RVA as the predominant strain in Indonesia in 2015-2016. However, since July 2017, typical human genotypes G1 and G3 have replaced these strains completely.

C-H functionalization of camphor through emerging approaches.

Camphor and related monoterpenoid natural products have served as versatile "chiral pool" materials in organic chemistry for over half a century. Historically, many researchers have used a variety of transformations involving orchestrated rearrangements of the bornane skeleton to functionalize the camphor framework, expanding the utility of this chiral building block. Recent developments in C-H functionalization methodologies provide myriad opportunities to derivatize the camphor framework in a selective and predictable fashion.

Streptococcus canis transcriptomic modifications in host cell entry environments of human keratinocytes.

Background: Streptococcus canis is a commensal bacterium in companion animals. This microorganism can infect humans who have been in deep contact with or bitten by pet dogs, suggesting that the skin/soft tissue is one of infection entry sites. To understand pathological process in human cells, we aimed to determine S.

Neonatal Fc receptor is a functional receptor for classical human astrovirus.

Human astrovirus (HAstV) is a global cause of gastroenteritis in infants, the elderly, and the immunocompromised. However, the molecular mechanisms that control its susceptibility are not fully understood, as the functional receptor used by the virus has yet to be identified. Here, a genome-wide CRISPR-Cas9 library screen in Caco2 cells revealed that the neonatal Fc receptor (FcRn) can function as a receptor for classical HAstV (Mamastrovirus genotype 1).

The isolation of sclerotinin A as an anti-malarial compound by utilization of a global secondary metabolism regulator, laeA gene.

Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp.

One-step syntheses of diaza-dioxa-fenestranes via the sequential (3 + 2) cycloadditions of linear precursors and their structural analyses.

Fenestranes, in which four rings share one carbon atom, have garnered much attention because of their flattened quaternary carbon centers. In addition, the rigid and nonplanar structures of heteroatom-containing fenestranes are attractive scaffolds for pharmaceutical applications. We report one-step syntheses of diaza-dioxa-fenestranes via the sequential (3 + 2) cycloadditions.

Isolation of microorganisms from the feces of Kitasato Yakumo beef cattle as bioactive natural product producers.

We envisioned that the rumen of Kitasato Yakumo beef cattle would contain unique microorganisms which produce bioactive compounds as their defense response to the external environment. The variety of microorganisms were collected from the feces of Kitasato Yakumo beef cattle. We evaluated the biological activity of the culture broth of the isolated strains, proving the utility of our approach.

Genetic organization of an M protein trans-acting positive regulator (Mga) orthologue and its adjacent M-like protein (SCM) alleles in Streptococcus canis.

Objective: The purpose of this study was to identify the M protein trans-acting positive regulator (Mga) orthologue and its adjacent M-like protein (SCM) alleles in Streptococcus canis.

Results: Using the 39 SCM allele isolates and polymerase chain reaction-based amplification and sequencing, we obtained the deduced Mga amino acid (AA) sequences. The 22 Mga sequences in whole-genome sequences were obtained by searching the National Collection of Type Cultures 12,191(T) Mga sequence into the database.

A new polyene macrolide antibiotic, machidamycin, produced by Streptomyces sp. K22-0017.

A new polyene macrolide, machidamycin (1), and a known compound YS-822A (2), were obtained by physicochemical screening from a culture broth of Streptomyces sp. K22-0017. The structures were elucidated using MS and 1D/2D NMR analyses.

Late-stage benzenoid-to-troponoid skeletal modification of the cephalotanes exemplified by the total synthesis of harringtonolide.

Skeletal modifications enable elegant and rapid access to various derivatives of a compound that would otherwise be difficult to prepare. They are therefore a powerful tool, especially in the synthesis of natural products or drug discovery, to explore different natural products or to improve the properties of a drug candidate starting from a common intermediate. Inspired by the biosynthesis of the cephalotane natural products, we report here a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners - representing the reverse of the proposed biosynthesis (i.

Genetic diversity of murine norovirus populations less susceptible to chlorine.

High genetic diversity in RNA viruses contributes to their rapid adaptation to environmental stresses, including disinfection. Insufficient disinfection can occur because of the emergence of viruses that are less susceptible to disinfection. However, understanding regarding the mechanisms underlying the alteration of viral susceptibility to disinfectants is limited.

Seven draft genome sequences of strains, revealing reduced penicillin-G susceptibility.

We report seven draft genome sequences of strains revealing reduced penicillin-G susceptibility. The genomes measured 2.054-2.

Microscopic and molecular genetic analyses of morphological development of the actinomycete Actinoplanes missouriensis.

The survival strategy of members of the bacterial genus Actinoplanes is fascinating from morphological and evolutionary perspectives. A brief motile phase is incorporated in the filamentous and resting stages of the life cycle of Actinoplanes missouriensis. Spores either lie dormant or swim under different external conditions.

and activities of KSP-1007, a broad-spectrum inhibitor of serine- and metallo-β-lactamases, in combination with meropenem against carbapenem-resistant Gram-negative bacteria.

KSP-1007 is a novel bicyclic boronate-based broad-spectrum β-lactamase inhibitor and is being developed in combination with meropenem (MEM) for the treatment of infections caused by carbapenem-resistant Gram-negative bacteria, a global health concern, and here, we describe its characteristics. KSP-1007 exhibited low apparent inhibition constant ( ) values against all classes of β-lactamase, including imipenemase types and oxacillinase types from . Against 207 and 55 .

Re-discovery of MS-347a as a fungicide candidate through a new drug discovery platform with a multidrug-sensitive Saccharomyces cerevisiae screening system and the introduction of a global secondary metabolism regulator, laeA gene.

We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillus sp.

PurA is the main target of aurodox, a type III secretion system inhibitor.

Anti-microbial resistance (AMR) is one of the greatest threats to global health. The continual battle between the emergence of AMR and the development of drugs will be extremely difficult to stop as long as traditional anti-biotic approaches are taken. In order to overcome this impasse, we here focused on the type III secretion system (T3SS), which is highly conserved in many Gram-negative pathogenic bacteria.