title: Design, synthesis and antimicrobial activities of thiouracil derivatives containing triazolo-thiadiazole as SecA inhibitors.
abstract: A series of novel thiouracil derivatives containing a triazolo-thiadiazole moiety (7a-7l) have been synthesized by structural modifications on a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7d and 7g were also tested for their inhibitory activities against SecA ATPase due to their promising antimicrobial activities. The inhibitory activity of compound 7d was found to be higher than that of 2. Molecular docking work suggests that compound 7d might bind at a pocket close to the ATPase ATP-binding domain.
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China; College of Science, Agricultural University of Hebei, Baoding 071001, China.
authors.forename: Penglei
authors.initials: P
authors.lastname: Cui
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China. Electronic address: lixl@hbu.cn.
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302-4098, USA.
authors.forename: Mengyuan
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Chemistry and Center for Diagnostics and Therapeutics, Georgia State University, Atlanta, GA 30302-4098, USA.
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
authors.affiliation: College of Veterinary Medicine, Agricultural University of Hebei, Baoding 071001, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Chemical Biology of Hebei Province, College of Chemistry and Environmental Science, Hebei University, Baoding 071002, China. Electronic address: hua-todd@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D000069816:SEC Translocation Channels / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000081416:SecA Proteins; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013830:Thiadiazoles / Q000737:chemistry*; D013889:Thiouracil / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D000069816:SEC Translocation Channels; D013830:Thiadiazoles; D014230:Triazoles; D013889:Thiouracil; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins
keywords: Antibacterial activity; Molecular simulation; SecA inhibitors; Thiouracil; Triazolo-thiadiazole