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 / thiocarbohydrazones
Source:
Pharmaceuticals, 2023, 16, 3, 341-
Publisher:
MDPI
Funding / projects:
The Slovenian Research Agency with research project J1-4402 (A.P.) and research program P1-0012 (A.P.) as well as by a young researcher grant (B.H.).
TY - JOUR
AU - Cvijetić, Ilija N.
AU - Herlah, Barbara
AU - Marinković, Aleksandar
AU - Perdih, Andrej
AU - Bjelogrlić, Snežana K.
PY - 2023
UR - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6361
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
IS - 3
SP - 341
VL - 16
DO - 10.3390/ph16030341
ER -
@article{
author = "Cvijetić, Ilija N. 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",
number = "3",
pages = "341",
volume = "16",
doi = "10.3390/ph16030341"
}
Cvijetić, I. N., 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 IN, 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 N., 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 . .
