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 = 130 μM). Most compounds exhibited excellent inhibitory activity (IC50 = 19.8–184.2 μM). 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.
Original language | English |
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Pages (from-to) | 4081-4085 |
Number of pages | 5 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 26 |
Issue number | 16 |
DOIs | |
Publication status | Published - 2016 |
Externally published | Yes |
Keywords
- Anti-infective
- Benzo[d]oxazole
- Sortase A