Inventi Rapid: Med Chem

Inventi:prmc/113201/25

Design, Synthesis and Characterization of Novel Quinolone-Aryl Ether Analogues as Potential Anti Bacterial Agents

The present study reports the synthesis of novel quinolone derivatives and their evaluation for antibacterial activities. Structure–activity relationship (SAR) studies have showed that the 1,4-dihydro-4-oxo-3-pyridine carboxylic acid pharmacophore is essential for antibacterial activity. However, the rise of multidrug-resistant (MDR) pathogens has significantly reduced the clinical efficacy of several existing fluoroquinolones, thereby necessary for the development of new derivatives with enhanced potency, improved selectivity and activity against resistant strains. Structural modifications at positions N-1, C-7 and C-8 of the quinolone nucleus are known to modulate drug–target interactions, increase lipophilicity and improve cellular penetration, leading to superior biological activity. In this present work, lomefloxacin was employed as a prototype molecule for the synthesis of novel derivatives. The modification for this drug mainly involves an acylation reaction with chloroacetyl-chloride, resulting in the formation of N-(Chloroacetyl lomefloxacin) takes place. The modification is mainly done at C4 Position of the piperazine ring with a linker. The chloroacetyl chloride is a linker for the reaction. N-(Chloroacetyl lomefloxacin) Further reacts with substituted phenols to form aryl ether derivatives (3a-f). Here chlorine atomof thechloroacetyl group is replaced by an aryl ether moiety, by forming an ether bond. The synthesized compounds were characterized by melting point determination; elemental analysis, FT-IR, ¹H NMR and mass spectrometry and all spectral data were reported. Additionally, QSAR parameters such as calculated Log P and drug-likeness were determined for the synthesized compounds. Antibacterial activity was evaluated against Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) strains at four concentrations (0.25, 0.5, 0.75, and 1.0 mg/mL), using lomefloxacin as the standard drug for comparison. Among the series, compounds 3a and 3b exhibited significant antibacterial activity against both Staphylococcus aureus and Escherichia coli, demonstrating their potential as promising antibacterial agents....