In vitro investigating of anticancer activity of new 7-MEOTA-tacrine heterodimers.
A549 Cells
Acridines
/ chemical synthesis
Antineoplastic Agents
/ chemical synthesis
Cell Proliferation
/ drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Fibroblasts
/ drug effects
HL-60 Cells
Humans
Structure-Activity Relationship
Tacrine
/ chemistry
Thiourea
/ chemistry
7-MEOTA-tacrine heterodimers
HL-60
calf thymus DNA
human dermal fibroblasts
topoisomerases
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2019
Dec 2019
Historique:
entrez:
3
4
2019
pubmed:
3
4
2019
medline:
15
5
2019
Statut:
ppublish
Résumé
A combination of biochemical, biophysical and biological techniques was used to study calf thymus DNA interaction with newly synthesized 7-MEOTA-tacrine thiourea 12-17 and urea heterodimers 18-22, and to measure interference with type I and II topoisomerases. Their biological profile was also inspected in vitro on the HL-60 cell line using different flow cytometric techniques (cell cycle distribution, detection of mitochondrial membrane potential dissipation, and analysis of metabolic activity/viability). The compounds exhibited a profound inhibitory effect on topoisomerase activity (e.g. compound 22 inhibited type I topoisomerase at 1 µM concentration). The treatment of HL-60 cells with the studied compounds showed inhibition of cell growth especially with hybrids containing thiourea (14-17) and urea moieties (21 and 22). Moreover, treatment of human dermal fibroblasts with the studied compounds did not indicate significant cytotoxicity. The observed results suggest beneficial selectivity of the heterodimers as potential drugs to target cancer cells.
Identifiants
pubmed: 30938202
doi: 10.1080/14756366.2019.1593159
pmc: PMC6450562
doi:
Substances chimiques
7-methoxy-1,2,3,4-tetrahydroacridin-9-amine
0
Acridines
0
Antineoplastic Agents
0
Tacrine
4VX7YNB537
Thiourea
GYV9AM2QAG
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
877-897Références
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