title: Design, synthesis and antibacterial activities of thiouracil derivatives containing acyl thiourea as SecA inhibitors.
abstract: A series of novel thiouracil derivatives containing an acyl thiourea moiety (7a-7x) have been synthesized by structural modification of a lead SecA inhibitor, 2. All the compounds have been evaluated for their antibacterial activities against Bacillus amyloliquefaciens, Staphylococcus aureus, and Bacillus subtilis. Compounds 7c, 7m, 7u, 7v exhibited promising activities against above bacteria. Such four compounds were further tested for their inhibitory activity against SecA ATPase, and the results showed that compounds 7c and 7u had higher inhibitory activities than that of compound 2. Molecular docking work suggests that compound 7u 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* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000069977:Bacillus amyloliquefaciens / Q000187:drug effects; D001412:Bacillus subtilis / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D000069816:SEC Translocation Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000081416:SecA Proteins; D013211:Staphylococcus aureus / Q000187:drug effects; D013889:Thiouracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D000069816:SEC Translocation Channels; D013889:Thiouracil; D000251:Adenosine Triphosphatases; D000081416:SecA Proteins
keywords: Acyl thiourea; Antibacterial activity; Molecular simulation; SecA inhibitors; Thiouracil