Sanguinarine Enhances the Integrity of the Blood–Milk Barrier and Inhibits Oxidative Stress in Lipopolysaccharide-Stimulated Mastitis

Mastitis is a common clinical disease which threatens the welfare and health of dairy cows and causes huge economic losses. Sanguinarine (SG) is a plant-derived alkaloid which has many biological functions, including antibacterial and antioxidant properties. The present study attempted to evaluate the effect of SG on lipopolysaccharide (LPS)-induced oxidative stress reactions and explore its potential mechanisms. The expression profile of SG was analyzed by network pharmacology, and it was found that differentially expressed genes were mainly involved in the Wnt signaling pathway and oxidative stress through GO and KEGG enrichment. In in vitro experiments, the dosage of SG was non-toxic to mouse mammary epithelial cells (mMECs) (p > 0.05). SG not only inhibited the increase in ROS induced by LPS, but also enhanced the activity of antioxidant enzymes (p p p < 0.05). Conclusively, this study clarified the protective effect of SG on mastitis and provided evidence for new potential mechanisms. SG exerted its antioxidant function through activating Nrf2 and inhibiting the Wnt/β-catenin pathway, repairing the blood–milk barrier

Concise synthesis of pyrrolo[2,3-d]pyrimidine derivatives via the Cu-catalyzed coupling reaction

We reported a green and simple Cu-catalyzed method for the efficient synthesis of 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide as the key intermediate in the synthetic approaches to pyrrolo[2,3-d]pyrimidine derivatives from 5-bromo-2,4-dichloropyrimidine through two routes in four steps and five steps, respectively. This method provided green and economical approaches toward numerous pyrrolo[2,3-d]pyrimidine derivatives

Concise synthesis of pyrrolo[2,3-<i>d</i>]pyrimidine derivatives via the Cu-catalyzed coupling reaction

<p>We reported a green and simple Cu-catalyzed method for the efficient synthesis of 2-chloro-7-cyclopentyl-<i>N,N</i>-dimethyl-7H-pyrrolo[2,3-<i>d</i>]pyrimidine-6-carboxamide as the key intermediate in the synthetic approaches to pyrrolo[2,3-<i>d</i>]pyrimidine derivatives from 5-bromo-2,4-dichloropyrimidine through two routes in four steps and five steps, respectively. This method provided green and economical approaches toward numerous pyrrolo[2,3-<i>d</i>]pyrimidine derivatives.</p

The Discovery of Potentially Selective Human Neuronal Nitric Oxide Synthase (nNOS) Inhibitors: A Combination of Pharmacophore Modelling, CoMFA, Virtual Screening and Molecular Docking Studies

Neuronal nitric oxide synthase (nNOS) plays an important role in neurotransmission and smooth muscle relaxation. Selective inhibition of nNOS over its other isozymes is highly desirable for the treatment of neurodegenerative diseases to avoid undesirable effects. In this study, we present a workflow for the identification and prioritization of compounds as potentially selective human nNOS inhibitors. Three-dimensional pharmacophore models were constructed based on a set of known nNOS inhibitors. The pharmacophore models were evaluated by Pareto surface and CoMFA (Comparative Molecular Field Analysis) analyses. The best pharmacophore model, which included 7 pharmacophore features, was used as a search query in the SPECS database (SPECS®, Delft, The Netherlands). The hit compounds were further filtered by scoring and docking. Ten hits were identified as potential selective nNOS inhibitors