Design, synthesis and exploration of novel triazinoindoles as potent quorum-sensing inhibitors and radical quenchers.
Jyoti RasganiaRenu GavadiaNeetu SahuPinki SharmaNar S ChauhanVicky SaharanRajeev K KapoorKomal JakharPublished in: Future medicinal chemistry (2024)
Background: Antimicrobial resistance has become a critical health concern, and quorum-sensing exacerbates the resistance by facilitating cell-to-cell communication within the microbial community, leading to severe pathogenic outbreaks. Methods & results: Novel 1-(2-((5 H -[1,2,4]-triazino[5,6- b ]indol-3-yl)thio)acetyl)indoline-2,3-diones were synthesized. The title compounds exhibit outstanding anti-quorum-sensing efficacy, and compound 7g demonstrated the maximum proficiency (IC 50 = 0.0504 μg/ml). The hybrids displayed potent antioxidant action, and compound 7c showed the highest antioxidant ability (IC 50 = 40.71 μg/ml). Molecular docking of the isatin hybrids against DNA gyrase and quorum-sensing receptor CviR validated the observed in vitro findings. The befitting pharmacokinetic profile of the synthesized drug candidates was ascertained through absorption, distribution, metabolism, excretion and toxicity screening. Conclusion: The remarkable biocompetence of the synthesized triazinoindoles may help to combat drug-resistant infections.
Keyphrases
- drug resistant
- microbial community
- molecular docking
- antimicrobial resistance
- oxidative stress
- multidrug resistant
- single cell
- anti inflammatory
- cell therapy
- public health
- acinetobacter baumannii
- healthcare
- molecular dynamics simulations
- oxide nanoparticles
- single molecule
- mesenchymal stem cells
- risk assessment
- health information
- drug induced
- circulating tumor
- bone marrow
- binding protein
- electronic health record
- human health