[1,2,4]Triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4',3'-c]quinazoline derived DNA intercalators: Design, synthesis, in silico ADMET profile, molecular docking and anti-proliferative evaluation studies.
Animals
Antineoplastic Agents
/ chemical synthesis
Cattle
Cell Line, Tumor
Cell Proliferation
/ drug effects
DNA
/ chemistry
Dose-Response Relationship, Drug
Drug Design
Drug Screening Assays, Antitumor
Humans
Molecular Docking Simulation
Molecular Structure
Quinazolines
/ chemical synthesis
Structure-Activity Relationship
Anticancer agents
Bis([1,2,4]triazolo)[4,3-a:4′,3′-c]quinazoline
DNA intercalators
Molecular docking
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
13
08
2020
revised:
10
12
2020
accepted:
11
12
2020
pubmed:
29
12
2020
medline:
31
7
2021
entrez:
28
12
2020
Statut:
ppublish
Résumé
In view of their DNA intercalation activities as anticancer agents, novel fifteen [1,2,4]triazolo[4,3-c]quinazoline and bis([1,2,4]triazolo)[4,3-a:4',3'-c]quinazoline derivatives have been designed, synthesized and evaluated against HepG2 and HCT-116. The molecular design was performed to investigate the binding mode of the proposed compounds with DNA active site. The data obtained from biological testing highly correlated with that obtained from molecular modeling studies. HCT-116 was found to be more sensitive cell lines to the influence of the new derivatives. In particular, compounds 16, 18, 11 and 5 were found to be the most potent derivatives with IC
Identifiants
pubmed: 33360576
pii: S0968-0896(20)30788-4
doi: 10.1016/j.bmc.2020.115958
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Quinazolines
0
DNA
9007-49-2
calf thymus DNA
91080-16-9
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
115958Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.