New thiazol-hydrazono-coumarin hybrids targeting human cervical cancer cells: Synthesis, CDK2 inhibition, QSAR and molecular docking studies.
Antineoplastic Agents
/ chemical synthesis
Apoptosis
/ drug effects
Cell Cycle
/ drug effects
Cell Proliferation
/ drug effects
Coumarins
/ chemistry
Cyclin-Dependent Kinase 2
/ antagonists & inhibitors
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Hydrazones
/ chemistry
Molecular Docking Simulation
Molecular Structure
Protein Kinase Inhibitors
/ chemical synthesis
Quantitative Structure-Activity Relationship
Thiazoles
/ chemistry
Tumor Cells, Cultured
2-Aminothiazole
CDK2 enzyme
Cell cycle arrest
HeLa cell line
Molecular docking
QSAR
Journal
Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
13
07
2018
revised:
18
12
2018
accepted:
16
01
2019
pubmed:
28
1
2019
medline:
1
4
2020
entrez:
28
1
2019
Statut:
ppublish
Résumé
Motivated by the potential anticancer activity of both coumarin and 2-aminothiazole nuclei, a new set of thiazol-2-yl hydrazono-chromen-2-one analogs were efficiently synthesized aiming to obtain novel hybrids with potential cytotoxic activity. MTT assay investigated the significant potency of all the target compounds against the human cervical cancer cell lines (HeLa cells). Cell cycle analysis showed that the representative compound 8a led to cell cycle cessation at G0/G1 phase indicating that CDK2/E1complex could be the plausible biological target for these newly synthesized compounds. Thus, the most active compounds (7c and 8a-c) were tested for their CDK2 inhibitory activity. The biological results revealed their significant CDK2 inhibitory activity with IC
Identifiants
pubmed: 30685646
pii: S0045-2068(18)30713-2
doi: 10.1016/j.bioorg.2019.01.026
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Coumarins
0
Hydrazones
0
Protein Kinase Inhibitors
0
Thiazoles
0
coumarin
A4VZ22K1WT
CDK2 protein, human
EC 2.7.11.22
Cyclin-Dependent Kinase 2
EC 2.7.11.22
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
80-96Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.