Aminoadamantanes containing monoterpene-derived fragments as potent tyrosyl-DNA phosphodiesterase 1 inhibitors

• Published in: Bioorganic chemistry Vol. 76; pp. 392 - 399
• Main Authors: Ponomarev, Konstantin Yu, Suslov, Evgeniy V., Zakharenko, Alexandra L., Zakharova, Olga D., Rogachev, Artem D., Korchagina, Dina V., Zafar, Ayesha, Reynisson, Jóhannes, Nefedov, Andrey A., Volcho, Konstantin P., Salakhutdinov, Nariman F., Lavrik, Olga I.
• Format: Journal Article
• Language: English
• Published: SAN DIEGO Elsevier Inc 01.02.2018; Elsevier
• Subjects: Adamantane - analogs & derivatives; Adamantane - chemical synthesis; Adamantane - chemistry; Adamantane - pharmacology; Adamantanes; Amine; Amines - chemical synthesis; Amines - chemistry; Amines - pharmacology; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Binding Sites; Biochemistry & Molecular Biology; Chemical space; Chemistry; Chemistry, Organic; Cytotoxicity; Drug Screening Assays, Antitumor; Drug Synergism; Fluorescent assay; HCT116 Cells; Humans; Life Sciences & Biomedicine; Molecular Docking Simulation; Monoterpenes - chemical synthesis; Monoterpenes - chemistry; Monoterpenes - pharmacology; Natural products; Phosphodiesterase Inhibitors - chemical synthesis; Phosphodiesterase Inhibitors - chemistry; Phosphodiesterase Inhibitors - pharmacology; Phosphoric Diester Hydrolases - chemistry; Phosphoric Diester Hydrolases - metabolism; Physical Sciences; Science & Technology; Stereoisomerism; Tdp1, molecular modelling; Topotecan - pharmacology; CXTYQHBRDVJROL-UHEPKEFZSA-N; Chemical space; Adamantanes; Amine; XNQOUINXDUSWSQ-UHFFFAOYSA-N; Natural products; Tdp1, molecular modelling; Cytotoxicity; Fluorescent assay; 2-AMINOADAMANTANE DERIVATIVES; EMPIRICAL SCORING FUNCTIONS; CAMPTOTHECINS; TOPOISOMERASE-I; CANCER; PROTEIN-LIGAND DOCKING; DATA-BANK; BIOLOGICAL EVALUATION; ADAMANTANE DERIVATIVES; TDP1 INHIBITORS

[Display omitted] •Aminoadamantane and monoterpene hybrids are good inhibitors of Tdp1.•The most promising inhibitor was synthesized from 1-aminoadamantane and citronellal.•The inhibitor enhanced cytotoxicity of topotecan against colon carcinoma HCT-116.•The inhibitor proved to have low own cytotoxi...