New N-amino-5-cyano-6-pyridones as antimicrobial small molecules endowed with DNA gyrase a inhibitory activity: design, one-pot synthesis, biological assessment and in silico insights
Year: 2024
Type: article
Abstract: A set of innovative N -amino-5-cyano-6-pyridones derivatives was developed and produced using one-pot three-component procedures. The evaluated molecules were examined for their antimicrobial efficacy. Based on the acquired findings, most of the investigated compounds had promising antimicrobial properties. Out of these derivatives of 3-cyanopyridine, compounds 3d and 3e exhibited minimum inhibitory concentrations (MIC) of 3.91 µg/mL against E.coli . In vitro evaluation of DNA gyrase A displayed that molecule 3d exhibited promising potency as an inhibitor, with an IC 50 value of 1.68 µg/mL compared to ciprofloxacin (IC 50 = 0.45 µg/mL). Furthermore, it was observed that molecule 3e exhibited a moderate inhibitory effect, as indicated by its IC 50 value of 3.77 µg/mL. A kinetics study conducted to assess the time required to kill E. coli bacteria demonstrated that gentamycin and compounds 3d and 3e exhibited bactericidal effects within a time frame of 90–120 min. Based on the ADME predictions, compounds 3d and 3e are expected to have favorable oral bioavailability and are unlikely to penetrate the blood-brain barrier. Computational mutagenicity and tumorigenicity studies were conducted on compounds 3d and 3e . The molecular docking investigation has conclusively demonstrated the binding of compounds 3d and 3e to the target DNA gyrase A enzyme, further reinforcing the existing data.
Source: BMC Chemistry
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,890
OpenAlex ID: W4404311201