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-1 H -pyrido[2,3- a ]carbazole-3-carboxylic acids ( 10b , 11b ) and 4-oxo-4,10-dihydro-1 H -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.