{"title":"双官能吡啶[2,3-b]吡嗪衍生物:生物活性及初步机制","authors":"Yong Zhang , Wenlei Chen , Dengyue Liu , Xiaoyan Zhao , Jixiang Chen","doi":"10.1016/j.pestbp.2025.106706","DOIUrl":null,"url":null,"abstract":"<div><div>To develop new antifungal and antibacterial agents, three derivatives containing pyrido[2,3-<em>b</em>]pyrazine were synthesized through derivation and optimization.</div><div>These derivatives exhibited excellent biological activities against 5 plant pathogenic fungal species (<em>Rhizoctonia solani</em>, <em>Phomopsis sp.</em>, <em>Botrytis cinerea</em>, <em>Sclerotinia sclerotiorum</em>, <em>and Magnaporthe oryzae</em>) and 3 plant pathogenic bacterial species (<em>Xanthomonas oryzae</em> pv. <em>oryzicola</em>, <em>Xanthomonas axonopodis</em> pv. <em>citri</em>, and <em>Pseudomonas syringae</em> pv. <em>actinidiae</em>). Among them, the EC<sub>50</sub> values of compound <strong>X2</strong> against the 5 plant pathogenic fungi were 3.15, 1.12, 0.69, 1.59, and 0.92 mg/L, respectively, which were significantly superior to those of fluopyram (192.29, 93.12, 42.23, 91.19, and 125.77 mg/L) and azoxystrobin (80.14, 25.14, 19.64, 36.81, and 59.51 mg/L). Its curative and protective activities against <em>B. cinerea</em> were 66.6 % and 60.3 %, respectively, which were significantly better than those of the positive controls fluopyram (27.0 % and 20.6 %) and azoxystrobin (60.1 % and 55.6 %). In addition, compound <strong>X2</strong> can inhibit mycelial growth, damage cell membranes, and increase intracellular ROS levels, thereby leading to the death of pathogenic fungi. The EC<sub>50</sub> values of <strong>X3</strong> against the 3 plant pathogenic bacteria were 0.13, 3.37, and 9.82 mg/L, respectively, which were significantly superior to those of thiodiazole‑copper and bismerthiazol. Its control effects on rice bacterial leaf streak were 40.79 % and 44.08 %, which were comparable to that of bismerthiazol (42.79 % and 46.35 %). Compound <strong>X3</strong> can inhibit the growth of pathogenic bacteria by inhibiting a variety of virulence factors (exopolysaccharides, biofilms, and motility). Therefore, pyrido[2,3-<em>b</em>]pyrazine can serve as a good scaffold to discover new antibacterial agents and fungicides.</div></div>","PeriodicalId":19828,"journal":{"name":"Pesticide Biochemistry and Physiology","volume":"216 ","pages":"Article 106706"},"PeriodicalIF":4.0000,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Difunctional pyrido[2,3-b]pyrazine derivatives: Biological activity and preliminary mechanism\",\"authors\":\"Yong Zhang , Wenlei Chen , Dengyue Liu , Xiaoyan Zhao , Jixiang Chen\",\"doi\":\"10.1016/j.pestbp.2025.106706\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>To develop new antifungal and antibacterial agents, three derivatives containing pyrido[2,3-<em>b</em>]pyrazine were synthesized through derivation and optimization.</div><div>These derivatives exhibited excellent biological activities against 5 plant pathogenic fungal species (<em>Rhizoctonia solani</em>, <em>Phomopsis sp.</em>, <em>Botrytis cinerea</em>, <em>Sclerotinia sclerotiorum</em>, <em>and Magnaporthe oryzae</em>) and 3 plant pathogenic bacterial species (<em>Xanthomonas oryzae</em> pv. <em>oryzicola</em>, <em>Xanthomonas axonopodis</em> pv. <em>citri</em>, and <em>Pseudomonas syringae</em> pv. <em>actinidiae</em>). Among them, the EC<sub>50</sub> values of compound <strong>X2</strong> against the 5 plant pathogenic fungi were 3.15, 1.12, 0.69, 1.59, and 0.92 mg/L, respectively, which were significantly superior to those of fluopyram (192.29, 93.12, 42.23, 91.19, and 125.77 mg/L) and azoxystrobin (80.14, 25.14, 19.64, 36.81, and 59.51 mg/L). Its curative and protective activities against <em>B. cinerea</em> were 66.6 % and 60.3 %, respectively, which were significantly better than those of the positive controls fluopyram (27.0 % and 20.6 %) and azoxystrobin (60.1 % and 55.6 %). In addition, compound <strong>X2</strong> can inhibit mycelial growth, damage cell membranes, and increase intracellular ROS levels, thereby leading to the death of pathogenic fungi. The EC<sub>50</sub> values of <strong>X3</strong> against the 3 plant pathogenic bacteria were 0.13, 3.37, and 9.82 mg/L, respectively, which were significantly superior to those of thiodiazole‑copper and bismerthiazol. Its control effects on rice bacterial leaf streak were 40.79 % and 44.08 %, which were comparable to that of bismerthiazol (42.79 % and 46.35 %). Compound <strong>X3</strong> can inhibit the growth of pathogenic bacteria by inhibiting a variety of virulence factors (exopolysaccharides, biofilms, and motility). Therefore, pyrido[2,3-<em>b</em>]pyrazine can serve as a good scaffold to discover new antibacterial agents and fungicides.</div></div>\",\"PeriodicalId\":19828,\"journal\":{\"name\":\"Pesticide Biochemistry and Physiology\",\"volume\":\"216 \",\"pages\":\"Article 106706\"},\"PeriodicalIF\":4.0000,\"publicationDate\":\"2025-09-24\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Pesticide Biochemistry and Physiology\",\"FirstCategoryId\":\"97\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0048357525004195\",\"RegionNum\":1,\"RegionCategory\":\"农林科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pesticide Biochemistry and Physiology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0048357525004195","RegionNum":1,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Difunctional pyrido[2,3-b]pyrazine derivatives: Biological activity and preliminary mechanism
To develop new antifungal and antibacterial agents, three derivatives containing pyrido[2,3-b]pyrazine were synthesized through derivation and optimization.
These derivatives exhibited excellent biological activities against 5 plant pathogenic fungal species (Rhizoctonia solani, Phomopsis sp., Botrytis cinerea, Sclerotinia sclerotiorum, and Magnaporthe oryzae) and 3 plant pathogenic bacterial species (Xanthomonas oryzae pv. oryzicola, Xanthomonas axonopodis pv. citri, and Pseudomonas syringae pv. actinidiae). Among them, the EC50 values of compound X2 against the 5 plant pathogenic fungi were 3.15, 1.12, 0.69, 1.59, and 0.92 mg/L, respectively, which were significantly superior to those of fluopyram (192.29, 93.12, 42.23, 91.19, and 125.77 mg/L) and azoxystrobin (80.14, 25.14, 19.64, 36.81, and 59.51 mg/L). Its curative and protective activities against B. cinerea were 66.6 % and 60.3 %, respectively, which were significantly better than those of the positive controls fluopyram (27.0 % and 20.6 %) and azoxystrobin (60.1 % and 55.6 %). In addition, compound X2 can inhibit mycelial growth, damage cell membranes, and increase intracellular ROS levels, thereby leading to the death of pathogenic fungi. The EC50 values of X3 against the 3 plant pathogenic bacteria were 0.13, 3.37, and 9.82 mg/L, respectively, which were significantly superior to those of thiodiazole‑copper and bismerthiazol. Its control effects on rice bacterial leaf streak were 40.79 % and 44.08 %, which were comparable to that of bismerthiazol (42.79 % and 46.35 %). Compound X3 can inhibit the growth of pathogenic bacteria by inhibiting a variety of virulence factors (exopolysaccharides, biofilms, and motility). Therefore, pyrido[2,3-b]pyrazine can serve as a good scaffold to discover new antibacterial agents and fungicides.
期刊介绍:
Pesticide Biochemistry and Physiology publishes original scientific articles pertaining to the mode of action of plant protection agents such as insecticides, fungicides, herbicides, and similar compounds, including nonlethal pest control agents, biosynthesis of pheromones, hormones, and plant resistance agents. Manuscripts may include a biochemical, physiological, or molecular study for an understanding of comparative toxicology or selective toxicity of both target and nontarget organisms. Particular interest will be given to studies on the molecular biology of pest control, toxicology, and pesticide resistance.
Research Areas Emphasized Include the Biochemistry and Physiology of:
• Comparative toxicity
• Mode of action
• Pathophysiology
• Plant growth regulators
• Resistance
• Other effects of pesticides on both parasites and hosts.