Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells.
AZT
Anticancer agents
Nucleosides
Tellurium
Triple negative
Journal
Bioorganic & medicinal chemistry letters
ISSN: 1464-3405
Titre abrégé: Bioorg Med Chem Lett
Pays: England
ID NLM: 9107377
Informations de publication
Date de publication:
01 09 2020
01 09 2020
Historique:
received:
20
05
2020
revised:
19
06
2020
accepted:
20
06
2020
entrez:
3
8
2020
pubmed:
3
8
2020
medline:
9
6
2021
Statut:
ppublish
Résumé
The present study aimed to investigate the effect of AZT derivates containing tellurium (Te) on human breast cancer cell lines and the mechanisms underlying cell death. The inhibitory effect of AZT and its derivatives (7m and 7r) was determined by the MTT assay (6.25, 12.5, 25, 50 and 100 μM in 24 and 48 h time points), meanwhile the induction of apoptosis and the cell cycle phases was investigated by flow cytometry. The MTT assay showed that AZT derivatives decreased the rate of cell proliferation at concentrations of 12.5 μM, while commercial AZT showed low antitumor potential. In flow cytometric analysis, we demonstrate that the AZT derivatives do not induce apoptosis at the concentration tested and promote the cell cycle arrest in the S phase. Besides, predicted absorption, distribution, metabolization, excretion and toxicity analysis suggest that the compounds possess a good pharmacokinetic profile and possibly less toxicity when compared to conventional AZT. These compounds containing tellurium in their formulation are potential therapeutic agents for breast cancer.
Identifiants
pubmed: 32738968
pii: S0960-894X(20)30476-5
doi: 10.1016/j.bmcl.2020.127365
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Zidovudine
4B9XT59T7S
Tellurium
NQA0O090ZJ
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127365Informations de copyright
Copyright © 2020. Published by Elsevier Ltd.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.