Background and the purpose of the study: Hospital-acquired methicillin-resistant Staphylococcus aureus (MRSA) has been a major problem worldwide in chemotherapy of infection disease. This study was designed to assess the enhancing effects of a new group of dihydropyridine-3,5-dicarboxamides, in combination with cloxacillin with distinctly different mechanisms of action against MRSAs.

Material and methods:Dihydropyridine-3,5-dicarboxamides with 2-methylsulfonylimidazole at 4 position 6a-k were synthesized by the reaction of corresponding aldehyde 5 with different N-aryl acetoacetamides 3 in the presence of ammonium hydroxide. Agar disc diffusion method was used to determine the antibacterial and potentiating activity of different synthetic compounds in the presence and absence of cloxacillin to evaluate their activity as modulators of multidrug-resistant (MDR).

Results and major conclusion: The antibacterial effect of cloxacillin was enhanced by compounds 6g and 6h against cloxacillin-resistant strains (MRSA1 and MRSA2). The potentiation was found to be statistically significant (p<0.01). Compound 6g at concentration of 1000 μg/disc, caused a 329 percent potentiation of the activity of cloxacillin against MRSA1.