The Development of Tyrosyl-DNA Phosphodiesterase 1 Inhibitors. Combination of Monoterpene and Adamantine Moieties via Amide or Thioamide Bridges

• Published in: Applied sciences Vol. 9; no. 13; p. 2767
• Main Authors: Chepanova, Arina A., Mozhaitsev, Evgenii S., Munkuev, Aldar A., Suslov, Evgeniy V., Korchagina, Dina V., Zakharova, Olga D., Zakharenko, Alexandra L., Patel, Jinal, Ayine-Tora, Daniel M., Reynisson, Jóhannes, Leung, Ivanhoe K. H., Volcho, Konstantin P., Salakhutdinov, Nariman F., Lavrik, Olga I.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.07.2019
• Subjects: A-549 lung adenocarcinoma cell line l; Cancer therapies; chemical space; Chromatography; Cytotoxicity; Deoxyribonucleic acid; DNA; Enzymes; fluorescence biosensor assay; intrinsic tryptophan fluorescence binding assay; Lung cancer; molecular modelling; Solvents; synergy; thermal shift assay; Topoisomerase 1; topotecan

Eleven amide and thioamide derivatives with monoterpene and adamantine substituents were synthesised. They were tested for their activity against the tyrosyl-DNA phosphodiesterase 1 DNA (Tdp1) repair enzyme with the most potent compound 47a, having an IC50 value of 0.64 µM. When tested in the A-549...