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DNA topoisomerase-directed anticancerous alkaloids: ADMET-based screening, molecular docking, and dynamics simulation.
Singh, Swati; Das, Tamal; Awasthi, Manika; Pandey, Veda P; Pandey, Brijesh; Dwivedi, Upendra N.
Afiliación
  • Singh S; Department of Biochemistry, Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, University of Lucknow, Lucknow, Uttar Pradesh, India.
  • Das T; Amity Institute of Biotechnology, Amity University, Lucknow, Uttar Pradesh, India.
  • Awasthi M; Department of Biochemistry, Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, University of Lucknow, Lucknow, Uttar Pradesh, India.
  • Pandey VP; Department of Biochemistry, Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, University of Lucknow, Lucknow, Uttar Pradesh, India.
  • Pandey B; Department of Biochemistry, Bioinformatics Infrastructure Facility, Center of Excellence in Bioinformatics, University of Lucknow, Lucknow, Uttar Pradesh, India.
  • Dwivedi UN; Amity Institute of Biotechnology, Amity University, Lucknow, Uttar Pradesh, India.
Biotechnol Appl Biochem ; 63(1): 125-37, 2016.
Article en En | MEDLINE | ID: mdl-25594242
Topoisomerases (Topo I and II) have been looked as crucial targets against various types of cancers. In the present paper, 100 anticancerous alkaloids were subjected to in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) analyses to investigate their pharmacokinetic properties. Out of 100 alkaloids, only 18 were found to fulfill all the ADMET descriptors and obeyed the Lipinski's rule of five. All the 18 alkaloids were found to dock successfully within the active site of both Topo I and II. A comparison of the inhibitory potential of 18 screened alkaloids with those of selected drugs revealed that four alkaloids (oliveroline, coptisine, aristolactam, and piperine) inhibited Topo I, whereas six alkaloids (oliveroline, aristolactam, anonaine, piperine, coptisine, and liriodenine) inhibited Topo II more strongly than those of their corresponding drugs, topotecan and etoposide, respectively, with oliveroline being the outstanding. The stability of the complexes of Topo I and II with the best docked alkaloid, oliveroline, was further analyzed using 10 nSec molecular dynamics simulation and compared with those of the respective drugs, namely, topotecan and etoposide, which revealed stabilization of these complexes within 5 nSec of simulation with better stability of Topo II complex than that of Topo I.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alcaloides / Inhibidores de Topoisomerasa / Antineoplásicos Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: Biotechnol Appl Biochem Asunto de la revista: BIOQUIMICA / BIOTECNOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Alcaloides / Inhibidores de Topoisomerasa / Antineoplásicos Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Animals / Humans Idioma: En Revista: Biotechnol Appl Biochem Asunto de la revista: BIOQUIMICA / BIOTECNOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos