Assessment of the Cytotoxicity of Peptide Modifications of Doxorubicin on Tetrahymena pyriformis.

A N Pozdnyakova, E G Cheremnykh, O Yu Sokolov, N V Kost, K V Shevchenko, V P Shevchenko, I Yu Nagaev, L A Andreeva, N F Myasoedov

Doklady. Biochemistry and biophysics 2021 Mar

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The cytotoxicity of doxorubicin (Dox) and its peptide modifications Z-Gly-Pro-Dox and Boc-Gly-Pro-Dox were studied. Tetrahymena pyriformis was used as a test system, which made it possible, due to the short life cycle and high reproduction rate of ciliates, to trace their response to the effects of toxicants over several generations. It was found that peptide modification of the Dox molecule markedly reduces its cytotoxic and cytostatic effect. The Z-Gly-Pro-Dox modification has less cytotoxic and cytostatic effect compared to Boc-Gly-Pro-Dox. When determining the ability of drugs (at a concentration of 100 μM) to prevent bacterial contamination of samples, it was shown that the smallest degree of overgrowth was recorded in the presence of Dox (OD600nm 81.1). Boc-Gly-Pro-Dox also had a bacteriostatic effect, though less pronounced (OD600nm 93.8). The degree of overgrowth in the presence of Z-Gly-Pro-Dox was close to that of distilled water. The results obtained on ciliates did not contradict the data obtained in similar studies on mice.

Citation

A N Pozdnyakova, E G Cheremnykh, O Yu Sokolov, N V Kost, K V Shevchenko, V P Shevchenko, I Yu Nagaev, L A Andreeva, N F Myasoedov. Assessment of the Cytotoxicity of Peptide Modifications of Doxorubicin on Tetrahymena pyriformis. Doklady. Biochemistry and biophysics. 2021 Mar;497(1):104-107