{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Il'ina IV"],"funding":["Russian Foundation for Basic Research","Russian Science Foundation"],"pagination":["E3496"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7436013"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(15)"],"pubmed_abstract":["Two novel structural types of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors with hexahydroisobenzofuran <b>11</b> and 3-oxabicyclo [3.3.1]nonane <b>12</b> scaffolds were discovered. These monoterpene-derived compounds were synthesized through preliminary isomerization of (+)-3-carene to (+)-2-carene followed by reaction with heteroaromatic aldehydes. All the compounds inhibit the TDP1 enzyme at micro- and submicromolar levels, with the most potent compound having an IC<sub>50</sub> value of 0.65 μM. TDP1 is an important DNA repair enzyme and a promising target for the development of new chemosensitizing agents. A panel of isogenic clones of the HEK293FT cell line knockout for the <i>TDP1</i> gene was created using the CRISPR-Cas9 system. Cytotoxic effects of topotecan (Tpc) and non-cyt"],"journal":["Molecules (Basel, Switzerland)"],"pubmed_title":["Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1."],"pmcid":["PMC7436013"],"funding_grant_id":["19-13-00040","19-415-540002"],"pubmed_authors":["Reynisson J","Lavrik OI","Chepanova AA","Chand R","Il'ina IV","Zakharenko AL","Li-Zhulanov NS","Dyrkheeva NS","Ilina ES","Medvedev SP","Salakhutdinov NF","Ayine-Tora DM","Sidorenko AY","Volcho KP","Malakhova AA","Zakharova OD","Zakian SM","Korchagina DV"],"additional_accession":[]},"is_claimable":false,"name":"Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1.","description":"Two novel structural types of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors with hexahydroisobenzofuran <b>11</b> and 3-oxabicyclo [3.3.1]nonane <b>12</b> scaffolds were discovered. These monoterpene-derived compounds were synthesized through preliminary isomerization of (+)-3-carene to (+)-2-carene followed by reaction with heteroaromatic aldehydes. All the compounds inhibit the TDP1 enzyme at micro- and submicromolar levels, with the most potent compound having an IC<sub>50</sub> value of 0.65 μM. TDP1 is an important DNA repair enzyme and a promising target for the development of new chemosensitizing agents. A panel of isogenic clones of the HEK293FT cell line knockout for the <i>TDP1</i> gene was created using the CRISPR-Cas9 system. Cytotoxic effects of topotecan (Tpc) and non-cyt","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2026-04-30T07:42:36.517Z","creation":"2026-04-07T15:54:46.729Z"},"accession":"S-EPMC7436013","cross_references":{"pubmed":["32751997"],"doi":["10.3390/molecules25153496"]}}