title: Synthesis and antifungal activity of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives as pyruvate dehydrogenase complex E1 inhibitors.
abstract: To identify new antifungal lead compound based on inhibitors of pyruvate dehydrogenase complex E1, a series of 5-iodo-1,4-disubstituted-1,2,3-triazole derivatives 3 were prepared and evaluated for their Escherichia coli PDHc-E1 inhibitory activity and antifungal activity. The in vitro bioassay for the PDHc-E1 inhibition indicated all the compounds exhibited significant inhibition against E. coli PDHc-E1 (IC50<21μM), special compound 3g showed the most potent inhibitory activity (IC50=4.21±0.11μM) and was demonstrated to act as a competitive inhibitor of PDHc-E1. Meanwhile, inhibitor 3g exhibited very good enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli. The assay of antifungal activity showed compounds 3e, 3g, and 3n exhibited fair to good activity against Rhizoctonia solani and Botrytis cinerea even at 12.5μg/mL. Especially compound 3n (EC50=5.4μg/mL; EC90=21.1μg/mL) exhibited almost 5.50 times inhibitory potency against B. cinerea than that of pyrimethanil (EC50=29.6μg/mL; EC90=113.4μg/mL). Therefore, in this study, compound 3n was found to be a novel lead compound for further optimization to find more potent antifungal compounds as microbial PDHc-E1 inhibitors.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China; College of Food Science & Engineering, Wuhan Polytechnic University, Wuhan 430023, China; Hubei Collaborative Innovation Center for Processing of Agricultural Products, Wuhan 430023, China.
authors.forename: Jun-Bo
authors.initials: JB
authors.lastname: He
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: He
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China.
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China.
authors.forename: Ge-Yun
authors.initials: GY
authors.lastname: You
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China.
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Feng
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China. Electronic address: jianwan@mail.ccnu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Wan
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University, Wuhan 430079, China. Electronic address: he1208@mail.ccnu.edu.cn.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: He
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D030481:Pyruvate Dehydrogenase (Lipoamide) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D012232:Rhizoctonia / Q000187:drug effects; D013552:Swine; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D011768:Pyruvate Dehydrogenase Complex; D014230:Triazoles; D030481:Pyruvate Dehydrogenase (Lipoamide)
keywords: 5-Iodo-1,4-disubstituted-1,2,3-triazole; Antifungal activity; Inhibitor; Pyruvate dehydrogenase complex