Novel inhibitors of bacterial two-component systems with gram positive antibacterial activity: Pharmacophore identification based on the screening hit closantel

Article abstract of DOI:10.1016/S0960-894X(98)00326-6

This SAR study has shown that the salicylanilide is the pharmacophore for inhibition of the bacterial two-component system. Hydrophobic substituents improve the potency of inhibitors in this series; however, hydrophobicity is not the sole determinant for inhibition; structural and electronic requirements also exist. Closantel (1) was found to inhibit a two- component system and to have antibacterial activity against drug resistant S. aureus and E. faecium.