UNASSIGNED: @entity794 sortase A is an attractive target of Gram-positive bacteria that plays a crucial role in anchoring of surface proteins to peptidoglycan present in bacterial cell wall. Inhibiting sortase A is an elementary and essential effort in preventing the pathogenesis. In this context, in silico virtual screening of in-house database was performed using ligand based pharmacophore model as a filter. The developed pharmacophore model AAHR 11 consists of two acceptors, one hydrophobic and one ring aromatic feature. Top ranked molecule KKR1 was docked into the active site of the target. After profound analysis, it was analyzed and optimized based on the observations from its binding pose orientation. Upgraded version of KKR1 was KKR2 and has improved docking score, binding interactions and best fit in the binding pocket. KKR1 along with KKR2 were further validated using 100ns molecular dynamic studies. Both KKR1 and KKR2 contain @entity104 - @entity19804 moiety and were synthesized. The disk diffusion assay has good initial results (ZI of KKR1, KKR2 were 24, 38mm at 10 g/mL and ZI of @entity869 was 22 at 10 g/mL) and calculated MICs of the molecules (KKR1 5.56  0.28 g/mL, KKR2 1.32  0.12 g/mL, Ampicillin 8  1.1 g/mL) were in good agreement with standard drug Ampicillin. KKR1 has shown IC50 of 1.23  0.14 M whereas the optimized lead molecule KKR2 show IC50 of 0.008  0.07 M. Results from in silico were validated by in vitro studies and proved that @entity104 - @entity19804 molecules would be useful for future development as lead molecules against @entity794 sortase A.

Designing of potential inhibitors against XXXX sortase A: Combined analogue and structure based approach with in vitro validation.

@entity869 :: ('MESH:D000667', 'Chemical') :: ['Ampicillin'] @entity19804 :: ('CHEBI:35622', 'Chemical') :: ['thiazolidine'] @entity794 :: ('1280', 'Species') :: ['Staphylococcus aureus', 'S. aureus'] @entity104 :: ('MESH:C030374', 'Chemical') :: ['indole', 'Indole']
@entity794 :: (1280,Species) :: ['Staphylococcus aureus']
