New bis(thieno[2,3-b]pyridine) hybrids linked to arene units as potential bacterial biofilm and MRSA inhibitors

Abstract

Using sonication and mediated by piperazine, new arene-linked bis(thieno[2,3- b]pyridine) hybrids were efficiently prepared in this study. The target hybrids were prepared by reacting bis(α-haloketone) with two equivalents of the appropriate pyridine-2(1H)-thiones in the presence of 1.4 equivalents of piperazine. The reaction mixture was subjected to sonication at 60 °C for 30–40 min to produce the desired products in 88%–95% yields. When tested against six different ATCC bacterial strains, the new products demonstrated a wide range of antibacterial activity. The 4-(4-methoxyphenyl)-linked hybrids 1i and 1j, attached to 6-(4-methoxyphenyl) and 6-( p-tolyl) units, respectively, had the best efficacy against Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa strains. Both hybrids showed more effective potency than the reference ciprofloxacin with MIC and MBC values in the ranges from 2.0 to 2.1, and 4.1 to 4.2 µM, respectively. Additionally, hybrids 1i and 1j demonstrated stronger efficacy than linezolid with MIC values ranging from 2.0 to 4.2 µM, and MBC values ranging from 8.2 to 8.5 µM, respectively, against the MRSA ATCC:33 591 and ATCC:43 300 strains. Furthermore, hybrids 1i and 1j showed inhibitory antibacterial biofilm activity comparable to the standard ciprofloxacin. They had IC50 values ranging from 3.8 to 4.6 µM against S. aureus, E. faecalis, E. coli, and P. aeruginosa strains. The cytotoxicity of hybrids 1i and 1j against the human breast epithelial cell line MCF-10A lends credence to both hybrids’ potential as safe antibacterial agents.