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Jun 24, 2020

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

Abstract

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.

By Adriely Maria, Oliveira Rocha, Fernanda Severo Sabedra Sousa, Victoria Mascarenhas Borba, Taiana S. Munchen, Julliano Guerin Leal, Oscar Endrigo, Dorneles Rodrigues, Mariana G. Fronza, Lucielli Savegnago, Tiago Collares, Fabiana Kömmling Seixas

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