New 3-(3-benzenesulfonylguanidinyl)thiourea derivatives with activity against methicillin-resistant Staphylococcus spp.

Methicilin-resistant staph, especially MRSA, has become major problems of modern epidemiology and chemotherapy. One of the methods of combating the growing resistance of bacterial strains is the search for new antibacterial agents. The numerous studies prove that the novel class of promising compounds with activity against Staphylococcus spp., including MRSA, comprises derivatives with thiosemicarbazide fragment. This encouraged us to the incorporation of the mentioned structural element to the benzensulfonamide skeleton. As a result, a series of new 3-(3-benzenesulfonylguanidinyl)thiourea derivatives were synthesized by nucleophilic addition of N-amino-N'-{4-chloro-5-methyl-2-[(3-trifluoromethylphenyl)methylthio]benzenesulfonyl}guanidine with appropriate isothiocyanates with variable R substituents.

The obtained derivatives were tested for antimicrobial activity against S. aureus and S. epidermidis, including MRSA and MRSE strains, using microdilution assay. All compounds displayed significant both bacteriostatic and bactericidal activity toward non-resistant strains (MIC in the range of 1.56 – 12.5 μg/ml; MBC in the range of 3.125 – 25 μg/ml for S. aureus and S. epidermidis). With regard to the methicillin-resistant strains, the effect was observed only for compound with R = 4-Cl-C₆H₄(MIC = 3.125 μg/ml against MRSA and MRSE, MBC = 3.125 and 6.25 μg/ml for MRSA and MRSE, respectively), however derivative with R = 3,4-(Cl₂)-C₆H₃ was bacteriostatic against MRSA (MIC = 3.125 μg/ml).