In Vitro and In Silico Studies of Human Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibition by Stereoisomeric Forms of Lipophilic Nucleosides: The Role of Carbohydrate Stereochemistry in Ligand-Enzyme Interactions.

Molecules (Basel, Switzerland) 2022 Apr 09

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Inhibition of human DNA repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1) by different chiral lipophilic nucleoside derivatives was studied. New Tdp1 inhibitors were found in the series of the studied compounds with IC50 = 2.7-6.7 μM. It was shown that D-lipophilic nucleoside derivatives manifested higher inhibition activity than their L-analogs, and configuration of the carbohydrate moiety can influence the mechanism of Tdp1 inhibition.

Citation

Nadezhda S Dyrkheeva, Irina A Chernyshova, Georgy A Ivanov, Yuri B Porozov, Anastasia A Zenchenko, Vladimir E Oslovsky, Alexandra L Zakharenko, Darina I Nasyrova, Galina N Likhatskaya, Sergey N Mikhailov, Olga I Lavrik, Mikhail S Drenichev. In Vitro and In Silico Studies of Human Tyrosyl-DNA Phosphodiesterase 1 (Tdp1) Inhibition by Stereoisomeric Forms of Lipophilic Nucleosides: The Role of Carbohydrate Stereochemistry in Ligand-Enzyme Interactions. Molecules (Basel, Switzerland). 2022 Apr 09;27(8)