A new quinolinone-chalcone hybrid with potential antibacterial and herbicidal properties using in silico approaches

• Published in: Journal of molecular modeling 2022-06, Vol.28 (6), p.176-176, Article 176
• Main Authors: Duarte, Vitor S., Paula, Renata L. G., Custodio, Jean M. F., D’Oliveira, Giulio D. C., Borges, Leonardo L., Pérez, Caridad N., Perjesi, Pal, Oliver, Allen G., Napolitano, Hamilton B.
• Format: Article
• Language: English
• Subjects: Aromatic compounds; Binding; Biological activity; Biological properties; Characterization and Evaluation of Materials; Chemical synthesis; Chemistry; Chemistry and Materials Science; Computer Appl. in Life Sciences; Computer Applications in Chemistry; Crystal growth; Efflux; Herbicides; Hybrid structures; Molecular Medicine; Molecular orbitals; Original Paper; Pharmacology; Pseudomonas putida; Stability analysis; Structural analysis; Sulfonamides; Theoretical and Computational Chemistry; Topology; VIII Symposium on Electronic Structure and Molecular Dynamics – VIII SeedMol
• ISSN: 1610-2940; 0948-5023
• DOI: 10.1007/s00894-022-05140-9

Quinolinone-chalcones are hybrid compounds consisting of chalcone and quinolone moieties with biological activity related to their hybrid structure. This work seeks to describe the structural and theoretical parameters related to the physicochemical properties and biological activity of a new quinolinone-chalcone. The synthesis, structural characterization by X-ray diffraction, molecular topology by Hirshfeld surfaces and QTAIM, molecular electronic calculations, and pharmacophore analysis were described. The weak interactions C–H … O, C–H … π, and C–H … Br were responsible for crystal growth and stabilized the crystalline state. The DFT analysis shows that the sulfonamide group region is susceptible to observed interactions, and the frontier molecular orbitals indicate high kinetic stability. Also, pharmacophore analysis revealed potential antibacterial and herbicidal activity; by docking within the active site of TtgR, a transcription regulator for the efflux pump TtgABC from the highly resistant Pseudomonas putida ( P. putida ) strain DOT-TIE, we showed that the activation of TtgR relies upon the binding of aromatic-harboring compounds, which plays a crucial role in bacterial evasion. In this context, a new quinolinone-chalcone has a higher binding affinity than tetracycline, which suggests it might be a better effector for TtgR.