Design, synthesis and antibacterial activity of novel pleuromutilin derivatives with thieno[2,3-d]pyrimidine substitution.

A series of novel pleuromutilin derivatives with substituted thienopyrimidines were designed, synthesized, and evaluated for antibacterial act ivity. In this study, the activities of these compounds were investigated using the inhibition circle test, the minimum inhibitory concentration (MIC) test, real-time growth curves, time-kill kinetic assays, cytotoxicity assays, and molecular docking. Most of the tested compounds exhibited moderate antibacterial activity against Staphylococcus aureus, Streptococcus agalactiae, and Escherichia coli. Compound A11 was the most active and displayed bacteriostatic activities against methicillin-resistant S. aureus, with MIC values as low as 0.00191 µg/mL, which is 162 and 32 times lower than that of the marketed antibiotics tiamulin and retapamulin, respectively. Furthermore, the mechanism of action of A11 was confirmed by molecular docking studies.

Pd-Catalyzed Rearrangement Reaction of N-Tosylhydrazones Bearing Allyl Ethers Into Trans-Olefin-Substituted Sulfonylhydrazones.

A novel and efficient rearrangement of N-tosylhydrazones bearing allyl ethers into trans-olefin-substituted sulfonylhydrazones is proposed. The reaction involves breakage of the C-O bond and formation of the C-N bond. The reaction can be extended to a wide range of substrates, and the target products can be synthesized smoothly, regardless of the presence of electron-donating and electron-withdrawing groups. The proposed strategy is a new direction in the field of rearrangement reactions.

Design, synthesis and biological evaluation of aminopyrimidine derivatives bearing a 4,5,6,7-tetrahydrothieno [3,2-c]pyridine as potent EGFR inhibitors.

To resolve the problem of drug resistance caused by epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer, we used the principle of collocation to design and synthesize a series of aminopyrimidine derivatives with 4,5,6,7-tetrahydrothieno [3,2-c]pyridine side chains (according to the binding mode of AZD9291 to EGFRT790M) for use as EGFRL858R/T790M kinase inhibitors. The most promising compound A12, a non-covalently bound reversible inhibitor, showed excellent kinase inhibitory activity against EGFRL858R/T790M, with an IC50 value of 4.0 nM and more than 42-fold selectivity for EGFRWT (IC50 = 170.0 nM). Moreover, compound A12 showed strong anti-proliferative activity against H1975 cells, with IC50 value of 0.086 µΜ. Additionally, the effective inhibition of cell migration and the promotion of apoptosis by A12 verified its mechanism of action, as a selective inhibitor of EGFRL858R/T790M.

Metal-Free Direct C-H Functionalization of Quinoxalin-2(1H)-Ones to Produce 3-Vinylated Quinoxalin-2(1H)-Ones in the Presence of Alkenes.

A novel and efficient C 3-H vinylation reaction with quinoxalin-2(1H)-one as the substrate, in the presence of alkenes, under metal-free conditions, is reported herein. The reaction leads to the formation of new carbon-carbon bonds that exhibit moderate to good reactivities. The vinylation of quinoxalin-2(1H)-ones, in the presence of alkenes, is an attractive process that can be potentially utilized to produce biologically active 3-vinylated quinoxalin-2(1H)-ones.

Light Pollution Changes the Toxicological Effects of Cadmium on Microbial Community Structure and Function Associated with Leaf Litter Decomposition.

Artificial light at night (ALAN/A) can not only alter the behavior and communication of biological organisms, it can also interact with other stressors. Despite its widespread use and the numerous potential ecological effects, little is known about the impact of ALAN on plant litter decomposition under cadmium (Cd) pollution in aquatic ecosystems. In an indoor microcosm experiment, we tested single and combined effects of ALAN and Cd on the activities and community structure of fungi associated with plant litter. The results showed that ALAN and/or Cd can change both water and leaf litter characteristics. ALAN exposure not only altered fungal community structure and their correlations, but also increased the activities of alkaline phosphatase, ß-glucosidase, and cellobiohydrolase. The leaf litter decomposition rate was 71% higher in the A-Cd treatment than that in the N-Cd treatment, indicating that the presence of ALAN weakened the negative impact of Cd on leaf litter decomposition. These results suggested that ALAN exposure mitigated the negative effect of Cd on leaf litter decomposition, contributing to the duel effect of ALAN on leaf litter decomposition. Overall, the results expand our understanding of ALAN on the environment and highlight the contribution of ALAN to Cd toxicity in aquatic ecosystems.