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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.

ABSTRACT: 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.

SUBMITTER: Dyrkheeva NS

PROVIDER: S-EPMC9024977 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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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.

Dyrkheeva Nadezhda S NS Chernyshova Irina A IA Ivanov Georgy A GA Porozov Yuri B YB Zenchenko Anastasia A AA Oslovsky Vladimir E VE Zakharenko Alexandra L AL Nasyrova Darina I DI Likhatskaya Galina N GN Mikhailov Sergey N SN Lavrik Olga I OI Drenichev Mikhail S MS

Molecules (Basel, Switzerland) 20220409 8

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 IC<sub>50</sub> = 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. ...[more]

PMID: 35458631

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