Synthesis and antibacterial activity of 8-nitro-7-(aryl/alkyl) and tetracyclic fluoroquinolones encompassing thiophene, furan, and related congeners

This work outlines the synthesis of six novel 8-nitro-7-(aryl/hetaryl)fluoroquinolones and five (aryl/hetaryl)tetracyclic fluoroquinolones; 4-oxo-4,11-dihydro-1H-pyrido[2,3-a]carbazole-3-carboxylic acids (10b, 11b) and 4-oxo-4,10-dihydro-1H-thieno/furo[4,5]pyrrolo[3,2-h]quinoline-3-carboxylic acids (3b–5b). The tetracyclic fluoroquinolone compounds were synthesized using a Suzuki–Miyaura cross-coupling acylation reaction of ethyl 7-chloro-1-cyclopropyl-6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate, followed by a microwave-assisted phosphite-mediated Cadogan reaction. The antibacterial activity of the compounds was evaluated against a range of Gram-negative bacteria, including Salmonella typhimurium, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, and Klebsiella aerogenes, as well as Gram-positive bacteria, including Listeria monocytogenes, Enterococcus faecalis, Streptococcus agalactiae, Staphylococcus aureus, and Staphylococcus epidermidis. The results demonstrated significant antibacterial activity against most of the tested strains. The lowest minimum inhibitory concentration (MIC) values observed were 7.7 μg/mL for compound 4b against S. agalactiae and compound 9b against S. aureus. These values are comparable to Streptomycin, which exhibited an MIC greater than 3.8 μg/mL for all tested pathogens.