title: Synthesis, biological evaluation and molecular docking of 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives as potential Staphylococcus aureus Sortase A inhibitors.
abstract: A series of novel 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives were designed, synthesized and evaluated for their in vitro inhibitory activities against Staphylococcus aureus Sortase A with known Sortase A inhibitor pHMB as positive compound (IC50=130μM). Most compounds exhibited excellent inhibitory activity (IC50=19.8-184.2μM). Structure-activity relationship studies demonstrated that substitution at 7-position and 2-position of benzoxazole had great influence on the activities. Specifically, the substituent at 7-position is indispensable for inhibitory activity. The molecular docking studies revealed the i-butyl amide group went towards the β6/β7 loop-β8 substructure of the protein and the benzoxazole core lied in a hydrophobic pocket composed of Ala118, Val166, Val168, Val169 and Ile182, shaping the whole molecule into a L-shape mode to be recognized by Sortase A.
authors.affiliation: School of Life Science and Biotechnology, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Bao
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China.
authors.forename: Xin-Xian
authors.initials: XX
authors.lastname: Deng
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China.
authors.forename: Wan
authors.initials: W
authors.lastname: He
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China.
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Fan
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China. Electronic address: jfq2008@sjtu.edu.cn.
authors.forename: Fa-Qin
authors.initials: FQ
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, No. 800 Dongchuan Rd., Shanghai 200240, PR China. Electronic address: leifu@sjtu.edu.cn.
authors.forename: Lei
authors.initials: L
authors.lastname: Fu
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001665:Binding Sites; D003546:Cysteine Endopeptidases / Q000378:metabolism; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D010080:Oxazoles / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013211:Staphylococcus aureus / Q000201:enzymology*; D055672:Static Electricity; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010080:Oxazoles; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases
keywords: Anti-infective; Benzo[d]oxazole; Sortase A