Chromene-based enaminones: Versatile precursors for the synthesis of new 1-phenyl-1 <i>H</i> -pyrazole-3-carboxylate hybrids with potential MRSA inhibitory potency
Mohamed A. A. Elneairy, Ahmed E. M. Mekky, Sherif M. H. Sanad, Nagwa H. S. Ahmed
Abstract
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.