Design, Synthesis, Antifungal Evaluation, and Three-Dimensional Quantitative Structure–Activity Relationship of Novel 5-Sulfonyl-1,3,4-thiadiazole Flavonoids

Article

作者: Dai, Peng ; Zhang, Weihua ; Ma, Zihua ; Li, Yufei ; Xia, Qing ; Jiao, Jian

Plant pathogenic fungi frequently disrupt the normal physiological and biochemical functions of plants, leading to diseases, compromising plant health, and ultimately reducing crop yield. This study aimed to address this challenge by identifying antifungal agents with innovative structures and novel mechanisms of action. We designed and synthesized a series of flavonoid derivatives substituted with 5-sulfonyl-1,3,4-thiadiazole and evaluated their antifungal activity against five phytopathogenic fungi. Most flavonoid derivatives demonstrated excellent antifungal activity against Botrytis cinerea (B. cinerea), Alternaria solani (A. solani), Rhizoctorzia solani (R. solani), Fusarium graminearum (F. graminearum), and Colletotrichum orbiculare (C. orbiculare). Specifically, the EC₅₀ values of 38 target compounds against R. solani were below 4 μg/mL, among which the compounds C13 (EC₅₀ = 0.49 μg/mL), C15 (EC₅₀ = 0.37 μg/mL), and C19 (EC₅₀ = 0.37 μg/mL) had the most prominent antifungal activity, superior to that of the control drug carbendazim (EC₅₀ = 0.52 μg/mL). Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of the cellular ultrastructures of R. solani mycelia and cells after treatment with the compound C19 revealed sprawling growth of hyphae, a distorted outline of their cell walls, and reduced mitochondrial numbers. Studying the 3D-QSAR between the molecular structure and antifungal activity of 5-sulfonyl-1,3,4-thiadiazole-substituted flavonoid derivatives could significantly improve conventional drug molecular design pathways and facilitate the development of novel antifungal leads.

2022-12-01·iScience

The ectromelia virus virulence factor C15 facilitates early viral spread by inhibiting NK cell contact

Article

作者: Peauroi, Elise M ; Reynoso, Glennys V ; Pei, Luxin ; Eisenlohr, Laurence C ; Carro, Stephen D ; Hickman, Heather D

The success of poxviruses as pathogens depends on their antagonism of host responses by multiple immunomodulatory proteins. The largest of these expressed by ectromelia virus (the agent of mousepox) is C15, one member of a well-conserved poxviral family previously shown to inhibit T cell activation. Here, we demonstrate by quantitative immunofluorescence imaging that C15 also limits contact between natural killer (NK) cells and infected cells in vivo. This corresponds to an inhibition in the number of total and degranulating NK cells, ex vivo and in vitro, with no detectable impact on NK cell cytokine production or the transcription of factors related to NK cell recruitment or activation. Thus, in addition to its previously identified capacity to antagonize CD4 T cell activation, C15 inhibits NK cell cytolytic function, which results in increased viral replication and dissemination in vivo. This work builds on a body of literature demonstrating the importance of early restriction of virus within the draining lymph node.

2022-11-01·Environmental Pollution

Responses of Alcanivorax species to marine alkanes and polyhydroxybutyrate plastic pollution: Importance of the ocean hydrocarbon cycles

Article

作者: Dong, Guihua ; Zhang, Baiyu ; Greer, Charles W ; Lee, Kenneth ; Chen, Bing ; Cai, Qinhong ; Liu, Bo ; Zhu, Zhiwen ; Cao, Yiqi

Understanding microbial responses to hydrocarbon and plastic pollution are crucial for limiting the detrimental impacts of environmental contaminants on marine ecosystems. Herein, we reported a new Alcanivorax species isolated from the North Atlantic Ocean capable of degrading alkanes and polyhydroxybutyrate (PHB) plastic (one of the emerging bioplastics that may capture the future plastic market). The whole-genome sequencing showed that the species harbors three types of alkane 1-monooxygenases (AlkB) and one PHB depolymerase (PhaZ) to initiate the degradation of alkanes and plastics. Growth profiling demonstrated that n-pentadecane (C15, the main alkane in the marine environment due to cyanobacterial production other than oil spills) and PHB could serve as preferential carbon sources. However, the cell membrane composition, PhaZ activity, and expression of three alkB genes were utterly different when grown on C15 and PHB. Further, Alcanivorax was a well-recognized alkane-degrader that participated in the ocean hydrocarbon cycles linking with hydrocarbon production and removal. Our discovery supported that the existing biogeochemical processes may add to the marine ecosystem's resilience to the impacts of plastics.

100 项与 C-0015 相关的药物交易

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