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Bioorg Med Chem Lett ; 30(17): 127365, 2020 09 01.
Article in English | MEDLINE | ID: mdl-32738968

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.


Subject(s)
Antineoplastic Agents/chemical synthesis , Zidovudine/analogs & derivatives , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Female , Half-Life , Humans , S Phase Cell Cycle Checkpoints/drug effects , Tellurium/chemistry , Triple Negative Breast Neoplasms/metabolism , Triple Negative Breast Neoplasms/pathology , Zidovudine/chemical synthesis , Zidovudine/pharmacokinetics , Zidovudine/pharmacology
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