Chromene-based enaminones: Versatile precursors for the synthesis of new 1-phenyl-1H-pyrazole-3-carboxylate hybrids with potential MRSA inhibitory potency

The goal of the current work is to explore the antibacterial potency, especially MRSA inhibitory activity, of new ethyl 4-(2-oxo-2H-chromene-3-carbonyl)-1-aryl-1H-pyrazole-3-carboxylates 1a-1l. The desired products are obtained, in 77–95% yields, by reacting the appropriate chromene-based enaminones with the various hydrazonyl chlorides utilizing a suitable [3 + 2] cycloaddition protocol. The aforementioned protocol was conducted using an equimolar amount of triethylamine in refluxing dioxane for 6–8 h. Some new chromene-pyrazoles showed promising bacterial inhibitory efficacy, especially against Staphylococcus aureus and Enterococcus faecalis. Ethyl 1-(4-nitrophenyl)-1H-pyrazole-3-carboxylate hybrids 1d and 1j, attached to 4-(6-(((4-chlorophenyl)thio)methyl)-2-oxo-2H-chromene-3-carbonyl) or 4-(2-oxo-6-((p-tolylthio)methyl)-2H-chromene-3-carbonyl) units, displayed comparable potency to ciprofloxacin with MIC/MBC of 2.2/4.4 and 2.3/4.6 µM, respectively. Moreover, the previous hybrids demonstrated comparable MRSA inhibitory potency to linezolid with MIC/MBC of 4.4/17.6 and 4.6/18.2 µM, respectively. As shown by the Ames test and in the presence of the S9 mix, 1d and 1j were found not to be mutagenic to Salmonella typhimurium strains.