Isothiazolopyridine Mannich bases and their antibacterial effect

Infections caused by multidrug-resistant (MDR) strains, i.e., strains resistant to at least 1 antibiotic of the 3 groups of antibacterial agents, are among the most difficult to treat. New compounds with an antimicrobial action are being sought in order to avoid the complete resistance of bacteria to drugs and the spread of MDR strains.

The aim of the research was to determine the antimicrobial activity of the new isothiazolopyridine derivatives.

All chemicals used were purchased from commercial suppliers. The 1H NMR spectra were recorded on a Bruker 300 MHz NMR spectrometer. Infrared (IR) spectra were run on a Perkin-Elmer Spectrum Two UATR FT-IR spectrometer (Perkin-Elmer, Waltham, USA). Elemental analyses were carried out on a Carlo Erba NA 1500 analyzer (Carlo Erba Reagents SAS, Val de Reuil, France). Melting points were determined with a Mel-Temp II apparatus (Laboratory Devices, Holliston, USA). The bacteria panel, including Escherichia coli ATCC 25922, Klebsiella pneumoniae ATCC 700603 (MDR), Acinetobacter baumannii ATCC 19606, Pseudomonas aeruginosa ATCC 27853, and multidrug-resistant Staphylococcus aureus ATCC 43300 (MRSA) were cultured in Muller-Hinton broth (MHB) at 37°C overnight. Colistin, Polymyxin B, Vancomycin, and Daptomycin were used as controls of bacterial inhibitors. Inhibition of bacterial growth was determined visually and was recorded at 32 μg/mL; 100% inhibition was identified.

The new dimethylisothiazolopyridines were prepared by the Mannich reaction. The structures of the isothiazolopyridines were determined based on spectral data analysis, such as IR and 1H NMR. The antimicrobial screening of new compounds was performed. In the primary screen, 2 compounds showed antimicrobial activity (minimum inhibitory concentration (MIC) ≤32 μg/mL).

Taking into account the obtained results, it should be stated that the examined compounds did not exceed the activity of reference drugs and, therefore, further research should be carried out in the group of isothiazolopyridine derivatives.