<abstract xmlns="http://www.w3.org/1999/xhtml">

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated <italic>in vitro</italic> and by <italic>in silico</italic> modeling. The compounds were more active against Gram-positive bacteria, <italic>Staphylococcus aureus</italic> (<italic>MIC</italic> = 0.026–0.226 mmol L−1) and <italic>Bacillus subtilis</italic> (<italic>MIC</italic> = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (<italic>MIC</italic> = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (<bold>1b</bold>) was found as active as imipenem against <italic>S. aureus</italic> (<italic>MIC</italic> = 0.026 mmol L–1). <italic>In silico</italic> docking of the compounds in the binding sites of a homology modeled structure of <italic>S. aureus</italic> histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of <bold>1b</bold> is consistent with its highest docking score values against <italic>S. aureus</italic> histidine kinase.
</abstract>

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone, or spiro-heterocycle moiety, was synthesized in a good yield. Chemical structures of the synthesized compounds were elucidated using spectroscopic techniques and elemental analysis. Antibacterial activities of the compounds were then evaluated in vitro and by in silico modeling. The compounds were more active against Gram-positive bacteria, Staphylococcus aureus (MIC = 0.026–0.226 mmol L−1) and Bacillus subtilis (MIC = 0.348–1.723 mmol L–1) than against Gram-negative bacteria (MIC = 0.817–7.393 mmol L–1). Only 3-hydroxy-3-(2-(2,5-dimethylthiophen-3-yl)-2-oxoethyl)indolin-2-one (1b) was found as active as imipenem against S. aureus (MIC = 0.026 mmol L–1). In silico docking of the compounds in the binding sites of a homology modeled structure of S. aureus histidine kinase-Walk allowed us to shed light on the binding mode of these novel inhibitors. The highest antibacterial activity of 1b is consistent with its highest docking score values against S. aureus histidine kinase.

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy

Department of Pharmaceutics, College of Pharmacy

Department of Microbiology and Immunology, Faculty of Pharmacy

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Longstanding and firsthand infectious diseases are challenging community health threats. A new series of isatin derivatives bearing β-hydroxy ketone, chalcone,...

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Pubblicato online: 30 ago 2021

Pagine: 79 - 95

Accettato: 17 gen 2021

DOI: https://doi.org/10.2478/acph-2022-0004

Parole chiave
2-indolinone, spiro[indole-heterocyles], antimicrobial, docking study

© 2022 Awwad Abdoh Radwan et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Design, synthesis and molecular modeling study of substituted indoline-2-ones and spiro[indole-heterocycles] with potential activity against Gram-positive bacteria

Pubblicato online: 30 ago 2021

Pagine: 79 - 95

Accettato: 17 gen 2021

DOI: https://doi.org/10.2478/acph-2022-0004

Parole chiave2-indolinone, spiro[indole-heterocyles], antimicrobial, docking study

© 2022 Awwad Abdoh Radwan et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Parole chiave
2-indolinone, spiro[indole-heterocyles], antimicrobial, docking study