Novel spiro[chromanone-2,4'-piperidine]-4-one derivatives as potential inhibitors of fatty acid synthesis in pathogens: Design, synthesis, and biological evaluation.

Bacterial survival depends on membrane lipid homeostasis that enables to regulate lipid composition to adapt and optimize their growth in diverse environments. Therefore, the development of inhibitors that interfere with the bacterial fatty acid synthesis process is considered to be a promising tactic. In this study, 58 novel spirochromanone derivatives were prepared and their structure-activity relationship (SAR) was investigated. The bioassay results showed that all most of the compounds showed excellent biological activities, exampled by compounds B14, C1, B15, and B13, which had outstanding inhibitory activities toward various pathogenic bacteria with EC50 values of 0.78 µg/mL ∼3.48 µg/mL. Preliminary antibacterial behavior was studied by a series of biochemical assays including, but not limited to, fluorescence imaging patterns, GC-MS analysis, TEM images, and fluorescence titration experiments. Notably, compound B14 decreased the lipid content of the cell membrane, and increased cell membrane permeability, thereby destroying the integrity of the bacterial cell membrane. Further qRT-PCR results indicated that compound B14 interfered with the mRNA expression levels of fatty acid synthesis process-related genes including ACC, ACP, and Fab family genes. Herein, we highlight the promising bactericidal skeleton based on the spiro[chromanone-2,4'-piperidine]-4-one as a potential inhibitor of fatty acid synthesis.

Novel cinnamic acid derivatives as a versatile tool for developing agrochemicals for controlling plant virus and bacterial diseases by enhancing plant defense responses.

BACKGROUND: Plant pathogens have led to large yield and quality losses in crops worldwide. The discovery and study of novel agrochemical alternatives based on the chemical modification of bioactive natural products is a highly efficient approach. Here, two series of novel cinnamic acid derivatives incorporating diverse building blocks with alternative linking patterns were designed and synthesized to identify their antiviral capacity and antibacterial activity. RESULTS: The bioassay results demonstrated that most cinnamic acid derivatives had excellent antiviral competence toward tobacco mosaic virus (TMV) in vivo, especially compound A5 (median effective concentration [EC50 ] = 287.7 µg mL-1 ), which had a notable protective effect against TMV when compared with the commercial virucide ribavirin (EC50  = 622.0 µg mL-1 ). In addition, compound A17 had a protective efficiency of 84.3% at 200 µg mL-1 against Xac in plants. Given these outstanding results, the engineered title compounds could be regarded as promising leads for controlling plant virus and bacterial diseases. Preliminary mechanistic studies suggest that compound A5 could enhance the host's defense responses by increasing the activity of defense enzymes and upregulating defense genes, thereby suppressing phytopathogen invasion. CONCLUSION: This research lays a foundation for the practical application of cinnamic acid derivatives containing diverse building blocks with alternative linking patterns in pesticide exploration. © 2023 Society of Chemical Industry.

Trickle-Down Effects of Entrepreneurial Bricolage and Business Model Innovation on Employee Creativity: Evidence From Entrepreneurial Internet Firms in China.

Although most existing studies have considered entrepreneurial bricolage as a means to overcome resource constraints in new ventures, few have explored the direct effects of entrepreneurial bricolage on employee creativity, particularly in the context of entrepreneurial internet firms. Drawing from multiple theories (i.e., social learning theory and social cognitive theory), this study proposes a cross-level mediation model for the trickle-down effects of entrepreneurial bricolage and business model innovation on employee creativity. By using a 2-wave longitudinal design, survey data were collected from multiple sources, including 49 leaders and 336 employees from entrepreneurial internet firms in China. Multilevel structural equation modeling (MSEM) was applied to analyze the cross-level mediation model. The results show that both entrepreneurial bricolage and business model innovation failed to significantly and positively direct employee creativity. Furthermore, entrepreneurial bricolage exerted a cross-level influence on employee creativity that was sequentially transmitted through between-level business model innovation and within-level creative self-efficacy. The theoretical and managerial implications of these findings are also discussed.