Antiproliferative and genotoxic potential of xanthen-3-one derivatives.
3T3 Cells
A549 Cells
Animals
Antineoplastic Agents
/ pharmacology
Cell Line
Cell Line, Tumor
Cell Proliferation
/ drug effects
Cytotoxins
/ pharmacology
DNA Damage
/ drug effects
Drug Screening Assays, Antitumor
/ methods
HeLa Cells
Hep G2 Cells
Humans
Mice
Molecular Docking Simulation
/ methods
Mutagens
/ pharmacology
Structure-Activity Relationship
antiproliferative activity
cytokinesis-block micronucleus cytome assay
docking study
genotoxic potential
xanthen-3-one derivatives
Journal
Acta pharmaceutica (Zagreb, Croatia)
ISSN: 1846-9558
Titre abrégé: Acta Pharm
Pays: Poland
ID NLM: 9303678
Informations de publication
Date de publication:
01 Dec 2019
01 Dec 2019
Historique:
accepted:
10
05
2019
entrez:
23
10
2019
pubmed:
23
10
2019
medline:
3
3
2020
Statut:
ppublish
Résumé
Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4' position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 4.1 µmol L-1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L-1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L-1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest.
Identifiants
pubmed: 31639090
doi: 10.2478/acph-2019-0044
pii: acph-2019-0044
doi:
Substances chimiques
Antineoplastic Agents
0
Cytotoxins
0
Mutagens
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
683-694Références
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