Antiproliferative Noscapinoids Bearing an Amidothiadiazole Scaffold as Apoptosis Inducers: Design, Synthesis and Molecular Docking.
Chem Biodivers
; 20(2): e202201089, 2023 Feb.
Article
em En
| MEDLINE
| ID: mdl-36690497
ABSTRACT
Noscapine an FDA-approved antitussive agent. With low cytotoxicity with higher concentrations, noscapine and its derivatives have been shown to have exceptional anticancer properties against a variety of cancer cell lines. In order to increase its potency, in this study, we synthesized a series of new amido-thiadiazol coupled noscapinoids and tested their cytotoxicity inâ
vitro. All of the newly synthesised compounds demonstrated potent cytotoxic potential, with IC50 values ranging from 2.1 to 61.2â
µM than the lead molecule, noscapine (IC50 value ranges from 31 to 65.5â
µM) across all cell lines, without affecting normal cells (IC50 value is>300â
µM). Molecular docking of all these molecules with tubulin (PDB ID 6Y6D, resolution 2.20â
Å) also revealed better binding affinity (docking score range from -5.418 to -9.679â
kcal/mol) compared to noscapine (docking score is -5.304â
kcal/mol). One of the most promising synthetic derivatives 6aa (IC50 value ranges from 2.5 to 7.3â
µM) was found to bind tubulin with the highest binding affinity (ΔGbinding is -28.97â
kcal/mol) and induced apoptosis in cancer cells more effectively.
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Base de dados:
MEDLINE
Assunto principal:
Antineoplásicos
/
Noscapina
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article