Design, synthesis, biological evaluation and molecular docking studies of some new quinoxaline azetidinone analogues

Quinoxaline and azetidinone (β-lactam) derivatives are well-known heterocyclic scaffolds possesses diverse biological activities, including antimicrobial, antioxidant, and antidiabetic properties. Owing to the growing need for novel and effective therapeutic agents to combat drug resistance and various metabolic disorders. In present study, we newly synthesized quinoxaline-azetidinone analogues and investigated the preliminary structure-activity relationship (SAR) studies of these compounds as antimicrobial, antioxidant, and antidiabetic activities. Fifteen quinoxaline-azetidinone analogues ( PQ 1 -PQ 15 ) were synthesized via a standard synthetic route and structurally characterized using FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectrometric analyses. The synthesized compounds were evaluated for in vitro antibacterial activity by the serial tube dilution method, antioxidant activity via the DPPH radical scavenging assay, and antidiabetic potential through the α-amylase inhibition assay. Antimicrobial screening identified PQ 9 as most active against E. coli (MIC = 0.42 µg/mL), while PQ 10 and PQ 11 showed strong activity against B. subtilis and S. aureus (MIC = 0.82 and 1.07 µg/mL), respectively. Among antifungal agents, PQ 2 and PQ 14 were most potent against A. niger and C. albicans (MIC = 0.17 and 1.72 µg/mL). PQ 12 exhibited the strongest antioxidant activity (IC 50 = 38.44 µM), and PQ 11 showed excellent antidiabetic potential via α-amylase inhibition (IC 50 = 29.21 µM). Molecular docking further confirmed PQ9’s highest binding affinity against S. aureus DNA gyrase (PDB ID: 2XCT), supporting its antibacterial potency. The newly synthesized hybrid compounds represent promising lead candidates for the development of novel antimicrobial, antioxidant, and antidiabetic agents.