Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα
Authors
Cvijetić, Ilija![](/themes/MirageCherry/images/orcid.png)
Herlah, Barbara
Marinković, Aleksandar
Perdih, Andrej
Bjelogrlić, Snežana K.
![](/themes/MirageCherry/images/orcid.png)
Article (Published version)
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Phenotypic screening of α-substituted thiocarbohydrazones revealed promising activity of 1,5-bis(salicylidene)thiocarbohydrazide against leukemia and breast cancer cells. Supplementary cell-based studies indicated an impairment of DNA replication via the ROS-independent pathway. The structural similarity of α-substituted thiocarbohydrazone to previously published thiosemicarbazone catalytic inhibitors targeting the ATP-binding site of human DNA topoisomerase IIα prompted us to investigate the inhibition activity on this target. Thiocarbohydrazone acted as a catalytic inhibitor and did not intercalate the DNA molecule, which validated their engagement with this cancer target. A comprehensive computational assessment of molecular recognition for a selected thiosemicarbazone and thiocarbohydrazone provided useful information for further optimization of this discovered lead compound for chemotherapeutic anticancer drug discovery.
Keywords:
cancer research / catalytic inhibitors / dynophores / human DNA topoisomerase IIα / molecular dynamics / phenotypic screening / thiocarbohydrazonesSource:
Pharmaceuticals, 2023, 16, 3, 341-Publisher:
- MDPI
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200168 (University of Belgrade, Faculty of Chemistry) (RS-MESTD-inst-2020-200168)
- Slovenian Research Agency with research project J1-4402 (A.P.) and research program P1-0012 (A.P.)
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Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Cvijetić, Ilija AU - Herlah, Barbara AU - Marinković, Aleksandar AU - Perdih, Andrej AU - Bjelogrlić, Snežana K. PY - 2023 UR - http://cherry.chem.bg.ac.rs/handle/123456789/6246 AB - Phenotypic screening of α-substituted thiocarbohydrazones revealed promising activity of 1,5-bis(salicylidene)thiocarbohydrazide against leukemia and breast cancer cells. Supplementary cell-based studies indicated an impairment of DNA replication via the ROS-independent pathway. The structural similarity of α-substituted thiocarbohydrazone to previously published thiosemicarbazone catalytic inhibitors targeting the ATP-binding site of human DNA topoisomerase IIα prompted us to investigate the inhibition activity on this target. Thiocarbohydrazone acted as a catalytic inhibitor and did not intercalate the DNA molecule, which validated their engagement with this cancer target. A comprehensive computational assessment of molecular recognition for a selected thiosemicarbazone and thiocarbohydrazone provided useful information for further optimization of this discovered lead compound for chemotherapeutic anticancer drug discovery. PB - MDPI T2 - Pharmaceuticals T1 - Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα VL - 16 IS - 3 SP - 341 DO - 10.3390/ph16030341 ER -
@article{ author = "Cvijetić, Ilija and Herlah, Barbara and Marinković, Aleksandar and Perdih, Andrej and Bjelogrlić, Snežana K.", year = "2023", abstract = "Phenotypic screening of α-substituted thiocarbohydrazones revealed promising activity of 1,5-bis(salicylidene)thiocarbohydrazide against leukemia and breast cancer cells. Supplementary cell-based studies indicated an impairment of DNA replication via the ROS-independent pathway. The structural similarity of α-substituted thiocarbohydrazone to previously published thiosemicarbazone catalytic inhibitors targeting the ATP-binding site of human DNA topoisomerase IIα prompted us to investigate the inhibition activity on this target. Thiocarbohydrazone acted as a catalytic inhibitor and did not intercalate the DNA molecule, which validated their engagement with this cancer target. A comprehensive computational assessment of molecular recognition for a selected thiosemicarbazone and thiocarbohydrazone provided useful information for further optimization of this discovered lead compound for chemotherapeutic anticancer drug discovery.", publisher = "MDPI", journal = "Pharmaceuticals", title = "Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα", volume = "16", number = "3", pages = "341", doi = "10.3390/ph16030341" }
Cvijetić, I., Herlah, B., Marinković, A., Perdih, A.,& Bjelogrlić, S. K.. (2023). Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα. in Pharmaceuticals MDPI., 16(3), 341. https://doi.org/10.3390/ph16030341
Cvijetić I, Herlah B, Marinković A, Perdih A, Bjelogrlić SK. Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα. in Pharmaceuticals. 2023;16(3):341. doi:10.3390/ph16030341 .
Cvijetić, Ilija , Herlah, Barbara, Marinković, Aleksandar, Perdih, Andrej, Bjelogrlić, Snežana K., "Phenotypic Discovery of Thiocarbohydrazone with Anticancer Properties and Catalytic Inhibition of Human DNA Topoisomerase IIα" in Pharmaceuticals, 16, no. 3 (2023):341, https://doi.org/10.3390/ph16030341 . .