Novel isoxazole–triazole conjugates have been efficiently synthesized using 3-formylchromone as starting material according to a multi-step synthetic approach. The structures of the target conjugates and intermediate products were characterized by standard spectroscopic techniques (¹H NMR and ¹³C NMR) and confirmed by mass spectrometry (MS). The all-synthesized compounds were screened for their antibacterial activity against three ATCC reference strains, namely Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC BAA-44, and Escherichia coli ATCC 25922 as well as one strain isolated from the hospital environment Pseudomonas aeruginosa. The findings indicate that conjugate 7b exhibits a stronger antibacterial response against the tested Escherichia coli ATCC 25922 and Pseudomonas aeruginosa pathogenic strains compared to the standard antibiotics. Furthermore, hybrid compound 7b proved to have a bactericidal action on the Escherichia coli ATCC 25922 strain, as evidenced by the results of the MBC determination. Moreover, the ADMET pharmacokinetic characteristics revealed a favorable profile for the examined compound, as well as a good level of oral bioavailability. Molecular docking and molecular dynamics simulations were performed to explore the inhibition mechanism and binding energies of conjugate 7b with the proteins of Escherichia coli and Pseudomonas aeruginosa bacterial strains. The in silico results corroborated the data observed in the in vitro evaluation for compound 7b.

In this study, we report the synthesis and biological evaluation of a novel series of chromone-isoxazoline hybrids. These conjugates were successfully synthesized through N-alkylation and 1,3-dipolar cycloaddition reactions, and their structures were determined by spectroscopic analysis (1H and 13C-NMR), mass spectrometry (MS), and X-ray diffraction (XRD) analysis. The XRD study showed that the compound crystallizes in the monoclinic system (S.G: P21/c). The antibacterial activity of the hybrid compounds was assessed in vitro against the Gram-positive bacterium Bacillus subtilis ATCC 6633 and three Gram-negative bacteria (Klebsiella aerogenes ATCC 13,048, Escherichia coli ATCC 27,853, and Salmonella enterica serotype Typhi) using the disk diffusion technique, MIC and MBC assays. The results showed that some tested compounds exhibited promising efficacy compared to the standard antibiotic chloramphenicol, underscoring their potential as antibacterial agents. These results were further validated through the determination of MIC and MBC values using the microdilution test, which showed a strong bactericidal effect of some compounds against the selected bacterial strains. Additionally, the studied compounds showed good anti-inflammatory potential by effectively inhibiting 5-LOX enzyme, with compound 5e was the most active, presenting an IC50 value of 0.951 ± 0.02 mg/mL. These in vitro results were complemented by in silico studies, including ADMET (absorption, distribution, metabolism, excretion, and toxicity) predictions and molecular docking simulations. The docking analyses provided insights into the inhibition mechanisms, revealing specific interactions of the synthesized molecules with target proteins relevant to both their antibacterial and anti-inflammatory activities. Finally, density functional theory (DFT)-based calculations were performed to optimize the geometric structures and analyze the structural and electronic properties of the hybrid compounds. While the results are promising, further optimization of compound potency is necessary to enhance their therapeutic potential.

Quinoline is a bicyclic aromatic heterocycle composed of a fused benzene and pyridine ring, and it has held an important place in medicinal chemistry for nearly two centuries. F. Runge first isolated it from coal tar in 1834, and it was later found to form the structural core of well-known natural products such as quinine, camptothecin, and γ-fagarine. Its asymmetric electron distribution, amphoteric character, and ability to undergo both electrophilic and nucleophilic substitution confer considerable pharmacophoric versatility on the quinoline scaffold. This review covers the chemistry and therapeutic relevance of quinoline derivatives, with an emphasis on their pharmacological significance rather than on their synthesis alone. It begins with a brief account of the scaffold’s structural features and main synthetic routes, then examines the biological activities reported for quinoline-based compounds, including antibacterial, anticancer, anti-inflammatory, antimalarial, antiparasitic, antitubercular, antioxidant, and antiviral activities, together with structure–activity relationships discussed at the level of specific ligand–target interactions where data allow. The last section covers more recent directions in quinoline-based drug discovery, including PROTAC degraders, kinase inhibitors, and multitarget-directed ligands, an area not extensively addressed in earlier reviews of this scaffold. The literature surveyed here shows that quinoline derivatives continue to serve as a versatile scaffold for generating new leads, linking established synthetic chemistry with current mechanistic and computational approaches. The continued diversification of quinoline-based chemotypes and their biological mechanisms reinforces the importance of this scaffold as a versatile platform for medicinal chemistry and drug discovery.