Synthesis and antifungal activity of 5-iodo-1, 4-disubstituted-1, 2, 3-triazole derivatives as pyruvate dehydrogenase complex E1 inhibitors. Issue 7 (1st April 2015)

• Record Type: Journal Article
• Authors: He, Jun-Bo; He, Hai-Feng; Zhao, Lu-Lu; Zhang, Li; You, Ge-Yun; Feng, Ling-Ling; Wan, Jian; He, Hong-Wu
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 7(2015)
• Page Start: 1395
• Page End: 1401
• Publication Date: 2015-04-01
• Subjects: 5-Iodo-1, 4-disubstituted-1, 2, 3-triazole -- Pyruvate dehydrogenase complex -- Inhibitor -- Antifungal activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.02.047
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: 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 derivatives3 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 <21 μM), special compound3g showed the most potent inhibitory activity (IC50 = 4.21 ± 0.11 μM) and was demonstrated to act as a competitive inhibitor of PDHc-E1. Meanwhile, inhibitor3g exhibited very good enzyme-selective inhibition of PDHc-E1 between pig heart and E. coli . The assay of antifungal activity showed compounds3e, 3g, and3n exhibited fair to good activity against Rhizoctonia solani and Botrytis cinerea even at 12.5 μg/mL. Especially compound3n (EC50 = 5.4 μg/mL; EC90 = 21.1 μg/mL) exhibited almost 5.50 times inhibitory potency against B. cinerea than that of pyrimethanil (EC50 = 29.6 μg/mL; EC90 = 113.4 μg/mL). Therefore, in this study, compound3n was found to be a novel lead compound for further optimization to find more potent antifungal compounds as microbial PDHc-E1 inhibitors.