Bacterial pathogens inflict substantial crop losses and economic damage, threatening global food security. Although antibacterial agents are available, their application is constrained by drug resistance, environmental hazards, and inadequate sustainability. Development of novel and effective antimicrobial agents has become urgent imperative. A series of morpholine-containing 1,3,4-thiadiazole derivatives were designed and synthesized. Compound H6 exhibited the most potent inhibitory activity against Xanthomonas oryzaepv oryzae (Xoo), with EC50 of 1.21 μg/mL-significantly lower than bismerthiazol (EC50 = 64.71 μg/mL) and thiodiazole-copper (EC50 = 63.94 μg/mL). Mechanistic studies revealed H6 inhibits biofilm and extracellular polysaccharide formation, disrupts membrane integrity, induces ROS accumulation, and promotes lipid peroxidation. Transcriptomic analysis demonstrated significant downregulation of key virulence genes (vgrG, accC, MCP), indicating attenuated pathogenicity. These results underscore H6 as a promising bactericidal agent, demonstrating considerable potential in sustainable management of plant bacterial diseases.
Mengzhi Yang, Chengpeng Li, Yue Zhou et al.· Journal of Agricultural and...· 0 citations
The high mortality rate of prostate cancer remains a major threat to men's health worldwide, highlighting an urgent need for novel therapeutic agents with improved efficacy and safety profiles. In this study, we employed a rational structural modification strategy to synthesize 14 novel 1,2,3-triazole-hybridized derivatives of piperlongumine (PL), a natural alkaloid with proven anticancer activity. The antiproliferative activity of these derivatives was evaluated in vitro against multiple cancer cell lines (PC-3, A549, T47D, and SMMC-7721), with normal HEK293 cells used to assess their selectivity. All synthesized derivatives (1 M-14 M) exhibited significant antitumor efficacy, with lead compound 11 M showing pronounced inhibition of PC-3 cell proliferation and migration. Mechanistic studies revealed that 11 M induced G2/M phase arrest and triggered mitochondrial-dependent apoptosis, while concurrently activating the ROS-MAPK signaling pathway and autophagic flux. Notably, 11 M attenuated DNMT3A-mediated global DNA hypomethylation. In vivo validation in PC-3 xenograft mice confirmed that 11 M exerted robust tumor growth suppression with low systemic toxicity, accompanied by DNMT3A downregulation and MAPK pathway activation, substantiating its multi-target therapeutic mechanism.