Your browser doesn't support javascript.
loading
Computational Approaches to Develop Isoquinoline Based Antibiotics through DNA Gyrase Inhibition Mechanisms Unveiled through Antibacterial Evaluation and Molecular Docking.
Alagumuthu, Manikandan; Muralidharan, Vivek Panyam; Andrew, Monic; Ahmed, Mohammed Habeeb; Iyer, Sathiyanarayanan Kulathu; Arumugam, Sivakumar.
Afiliación
  • Alagumuthu M; Dept. of Biotechnology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore-, 632014, India.
  • Muralidharan VP; Dept. of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore-, 632014, India.
  • Andrew M; Dept. of Biotechnology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore-, 632014, India.
  • Ahmed MH; Dept. of Biotechnology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore-, 632014, India.
  • Iyer SK; Dept. of Chemistry, School of Advanced Sciences, Vellore Institute of Technology, Vellore-, 632014, India.
  • Arumugam S; Dept. of Biotechnology, School of Bio-Sciences and Technology, Vellore Institute of Technology, Vellore-, 632014, India.
Mol Inform ; 37(12): e1800048, 2018 12.
Article en En | MEDLINE | ID: mdl-30051592
Developing a new antibacterial drug by using (Z/E)-4-(4-substituted-benzylidene)-2-isoquinoline-1,3(2H,4H)-diones (5a-h) via DNA gyrase inhibition mechanism is the main aim of this study. DNA gyrase inhibition assay was executed to confirm the DNA gyrase inhibition potentials of 5a-h. DNA gyrase inhibitory potentials were further validated through molecular docking. Docking study was also intended to get more insight into the binding mode of 5a-h into the active site of DNA gyrase A. Agar well diffusion method antimicrobial activity on Gram-ve bacteria Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 424), and Gram+ve bacteria (Staphylococcus aureus (MTCC 96) and Streptococcus pyogenes (MTCC 442) was evaluated. Excellent DNA gyrase inhibition was exhibited by the compound 5c, IC50 0.55±0.12 µM; 5d, IC50 0.65±0.075 µg/mL; 5e, IC50 0.45±0.035 µM; 5f, IC50 0.58±0.025 µM; 5h, IC50 0.25±0.015 µM while Clorobiocin (standard) showed IC50 0.5±0.05 µM. Apart from all the in vitro studies, a plausible mechanism of DNA gyrase inhibition was also proposed through the in silico validations that are including molecular docking, predicted SAR, functional group availability, pharmacokinetic, and ADMET properties. These predictions are well supported to confirm the druggability possibility of the most potent compounds among (Z/E)-4-(4-substituted-benzylidene)-2-isoquinoline-1,3(2H,4H) -diones (5a-h).
Asunto(s)
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Girasa de ADN / Descubrimiento de Drogas / Inhibidores de Topoisomerasa II / Simulación del Acoplamiento Molecular / Antibacterianos Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Inform Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Alemania
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Bacterianas / Girasa de ADN / Descubrimiento de Drogas / Inhibidores de Topoisomerasa II / Simulación del Acoplamiento Molecular / Antibacterianos Tipo de estudio: Prognostic_studies Idioma: En Revista: Mol Inform Año: 2018 Tipo del documento: Article País de afiliación: India Pais de publicación: Alemania