Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells.


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
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

127365

Informations 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.

Auteurs

Adriely Maria Oliveira Rocha (AM)

Postgraduate Program in Biotechnology (PPGB), Research Group on Cellular and Molecular Oncology - GPO, Center for Technological Development, Federal University of Pelotas, Pelotas, RS, Brazil.

Fernanda Severo Sabedra Sousa (F)

Postgraduate Program in Biotechnology (PPGB), Research Group on Cellular and Molecular Oncology - GPO, Center for Technological Development, Federal University of Pelotas, Pelotas, RS, Brazil.

Victoria Mascarenhas Borba (V)

Postgraduate Program in Biotechnology (PPGB), Research Group on Cellular and Molecular Oncology - GPO, Center for Technological Development, Federal University of Pelotas, Pelotas, RS, Brazil.

Taiana S Munchen (T)

Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.

Julliano Guerin Leal (J)

Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.

Oscar Endrigo Dorneles Rodrigues (OE)

Department of Biochemistry and Molecular Biology, Center for Natural and Exact Sciences, Federal University of Santa Maria, Santa Maria, RS, Brazil.

Mariana G Fronza (M)

Postgraduate Program in Biotechnology (PPGB), Neurobiotechnology Research Group, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil.

Lucielli Savegnago (L)

Postgraduate Program in Biotechnology (PPGB), Neurobiotechnology Research Group, Technological Development Center, Federal University of Pelotas, Pelotas, RS, Brazil.

Tiago Collares (T)

Postgraduate Program in Biotechnology (PPGB), Research Group on Cellular and Molecular Oncology - GPO, Center for Technological Development, Federal University of Pelotas, Pelotas, RS, Brazil.

Fabiana Kömmling Seixas (F)

Postgraduate Program in Biotechnology (PPGB), Research Group on Cellular and Molecular Oncology - GPO, Center for Technological Development, Federal University of Pelotas, Pelotas, RS, Brazil. Electronic address: seixas.fk@gmail.com.

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Classifications MeSH