New Deoxycholic Acid Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitors Also Inhibit Tyrosyl-DNA Phosphodiesterase 2

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 1; p. 72
• Main Authors: Salomatina, Oksana V., Dyrkheeva, Nadezhda S., Popadyuk, Irina I., Zakharenko, Alexandra L., Ilina, Ekaterina S., Komarova, Nina I., Reynisson, Jóhannes, Salakhutdinov, Nariman F., Lavrik, Olga I., Volcho, Konstantin P.
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 23.12.2021; MDPI
• Subjects: Acids; amide; Apoptosis; Binding Sites; cancer; Cancer therapies; Cell Line; Chemical Phenomena; Chemistry Techniques, Synthetic; Chromatography; Cytotoxicity; deoxycholic acid; Deoxycholic Acid - analogs & derivatives; Deoxycholic Acid - chemistry; Deoxycholic Acid - pharmacology; DNA repair; Enzyme Activation - drug effects; Enzymes; Humans; Models, Molecular; Molecular Conformation; Molecular Structure; Organic chemicals; oxadiazoles; Peptides; Phosphodiesterase Inhibitors - chemical synthesis; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - chemistry; Phosphoric Diester Hydrolases - metabolism; Protein Binding; Recombinant Proteins - chemistry; Steroids; Structure-Activity Relationship; TDP1 inhibitor; TDP2 inhibitor; TDP1 inhibitor; TDP2 inhibitor; amide; molecular modeling; tumor; oxadiazoles; cancer; deoxycholic acid

A series of deoxycholic acid (DCA) amides containing benzyl ether groups on the steroid core were tested against the tyrosyl-DNA phosphodiesterase 1 (TDP1) and 2 (TDP2) enzymes. In addition, 1,2,4- and 1,3,4-oxadiazole derivatives were synthesized to study the linker influence between a para-bromoph...