In this proposed investigation, we will exploit the concept of dimerization to overcome antibiotics resistance. Sulfonamide will be designed to covalently link to trimethoprim. We envision that the dimeric displayed antibacterial agents could enhance efficacy of the monomeric agents. The scope of our investigation would focus on global problematic pathogen S. aureus, particularly methicillin-susceptible S. aureus (MSSA) and multidrugs-resistant S. aureus.
In this study, we plan to follow these specific aims:
Aim 1. To design and synthesis dimeric ligand displaying sulfonamide and trimethoprim. The length of the linker between sulfonamide and trimethoprim will be varied to determine the effect of the linker to the efficacy observed.
Aim 2. To test for the ability of synthetic dimer to inhibit growth of MSSA and global predominant multidrug-resistant S. aureus. The susceptibility tests used in this study are disk diffusion assay and microdilution assay.
Aim 3. To investigate the mechanism of action underlying the growth inhibition activity.
