Synthesis, biological evaluation and molecular docking of 2-phenyl-benzo[d]oxazole-7-carboxamide derivatives as potential Staphylococcus aureus Sortase A inhibitors.

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 ß6/ß7 loop-ß8 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.

Purification and Functional Characterization of a Shark Cartilage Factor Inhibitory to Angiogenesis.

SCAIF-I, an inhibitor of angiogenesis from shark cartilage was purified to homogeneity. The 4 mol/L guanidinium chloride extract of shark cartilage was fractionally precipitated with 35%-65% acetone, then purified by Resource Q ion exchange chromatography, Sephacryl S-300 gel filtration, and reverse-phase high performance liquid chromatography. The pure inhibitor was homogeneous as a single band on a silver-stained 15% sodium dodecyl sulfate-polyacrylamide gel. SCAIF-I had an molecular weight of 18 kD. It specifically inhibited proliferation of endothelial cells, and strongly blocked endothelial cell movement and angiogenesis in the chorioallantoic membrane of chick embryos. Systemic administration of SCAIF-I at the dose of 5 mg/kg.d suppressed 87.93% of the growth of Lewis lung carcinoma implanted in C57BL/6 mice.