Quinolones represent one of the largest classes of synthetic antibiotics used in both human and veterinary medicine. Since the discovery of nalidixic acid, a substantial body of research has been carried out on quinolones, resulting in the synthesis of several quinolone derivatives with exceptional pharmacology. In addition to their antibacterial action, quinolones have a broad spectrum of diverse biological activities. In this regard, the present review examines the literature of recent years describing synthesis protocols, reactivity and biological properties, with particular emphasis on the antibacterial, antimalarial, antitrypanosomal, antileishmanial, antiviral and anticancer activities of this famous class of molecules. Finally, this review highlights the potential of quinolones as preferred pharmacophores in medicinal chemistry. The aim is to highlight the innovative aspects of the rational design of new therapeutic agents with this structural motif, in the face of emerging antibiotic resistance and the urgent need for new active molecules.

In the title molecule, C₁₄H₁₁NO₃, the dihydroquinoline core deviates slightly from planarity, indicated by the dihedral angle of 1.07 (3)° between the two six-membered rings. In the crystal, layers of molecules almost parallel to the bc plane are formed by C—H...O hydrogen bonds. These are joined by π–π stacking interactions. A Hirshfeld surface analysis revealed that the most important contributions to the crystal packing are from H...H (36.0%), H...C/C...H (28.9%) and H...O/O...H (23.5%) interactions. The evaluation of the electrostatic, dispersion and total energy frameworks indicates that the stabilization is dominated by the dispersion energy contribution. Moreover, the molecular structure optimized by density functional theory (DFT) at the B3LYP/6-311G(d,p) level is compared with the experimentally determined molecular structure in the solid state. The HOMO–LUMO behaviour was elucidated to determine the energy gap.

Quinolones represent one of the largest classes of synthetic antibiotics used in both human and veterinary medicine. Subsequent to the discovery of nalidixic acid, a substantial body of research has been carried out on quinolones, resulting in the synthesis of a number of quinolone derivatives with exceptional pharmacology. In addition to their antibacterial action, quinolones have a broad spectrum of diverse biological activities. In this regard, the present review examines the literature of recent years describing synthesis protocols, reactivity and biological properties, with particular emphasis on the antibacterial, antimalarial, antitrypanosomal, antileishmanial, antiviral and anticancer activities of these famous nuclei. Finally, this review highlights the potential of quinolones as preferred pharmacophores in medicinal chemistry. The aim is to highlight the innovative aspects of rationally designing new therapeutic agents with this structural motif, in the face of emerging antibiotic resistance and the urgent need for new active molecules.

The title compound, C₁₉H₁₄N₂O₃, features competition and interplay of a range of weak interactions, which actualize under the absence of conventional hydrogen-bond donors. Two kinds of stacking interactions, namely slipped antiparallel interactions of cyanophenyl groups as well as quinoline and carboxy groups, are primarily important. In combination with relatively short tetrel OCH₃...N[triple-bond]C bonds [C...N = 3.146 (3) Å] they are responsible for the generation of the layers, while the interlayer bonding occurs via C—H...O and C—H...N weak hydrogen bonds. These findings are consistent with the results of Hirshfeld surface analysis and calculated interaction energies. Contributions of the C...C, C...N/N...C and C...O/O...C contacts originating in the stacking interactions account for 17.0% to the surface area. The largest interactions energies are associated with the two kinds of stacks (−45.8 and −24.3 kJ mol⁻¹) and they are superior to the energies of weak hydrogen bond and tetrel interactions (−12.4 to −22.4 kJ mol⁻¹). Evaluation of the electrostatic, dispersion and total energy frameworks indicate that the consolidation is dominated via the dispersion energy contributions.

Background/Objectives: The rise in antibiotic resistance presents a serious and urgent global health challenge, emphasizing the need to develop new therapeutic compounds. This study focuses on the design and evaluation of a novel series of hybrid molecules that combine the 2-quinolone and 1,2,3-triazole pharmacophores, both recognized for their broad-spectrum antimicrobial properties. Methods: A library of 29 candidate molecules was first designed using in silico techniques, including QSAR modeling, ADMET prediction, molecular docking, and molecular dynamics simulations, to optimize antibacterial activity and drug-like properties. The most promising compounds were then synthesized and characterized by ¹H and ¹³C NMR APT, mass spectrometry (MS), Fourier-transform infrared (FT-IR) spectroscopy, and UV-Vis spectroscopy. Results: Antibacterial evaluation revealed potent activity against both Gram-positive and Gram-negative bacterial strains, with minimum inhibitory concentration (MIC) values ranging from 0.019 to 1.25 mg/mL. Conclusions: These findings demonstrate the strong potential of 2-quinolone–triazole hybrids as effective antibacterial agents and provide a solid foundation for the development of next-generation antibiotics to combat the growing threat of bacterial resistance.

Human african trypanosomiasis (HAT), commonly referred to as sleeping sickness, is a disease that originates from protozoan parasites of the Trypanosoma genus, which might be fatal if left untreated, or treated inadequately. Tsetse fly, a tropical blood-feeding insect, is generally the biological vector for this disease. Initially, the disease was neglected, however, when faced with the exploding number of cases, the urgent human needs for safe and cost-effective drugs combating the disease have increased significantly. The current study aims to computationally help advance the clinical care of HAT disease by leveraging computational tools to analyze the potential of quinolone amide derivatives to inhibit the enzyme responsible for this disease. The results demonstrate that jointly considering molecular affinity, polarity, and volume enables accurate inference of the bioactivity of quinolone derivatives, facilitating the efficient screening of large compound libraries. An effective QSAR model was developed using a dataset of 31 molecules, allowing reliable prediction of antitrypanosomal activity. Three promising compounds were identified based on their favorable physicochemical and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles, as well as their strong binding interactions with ornithine decarboxylase (ODC) complexed with putrescine (PDB: 1F3T). Finally, a straightforward synthetic route was proposed for a novel compound with high biological potential. Overall, the study shows that an in-silico study can be used to efficiently drive a Quinolone-based drug design to target the HAT disease.