Cu(II) complexes based on morpholine-substituted thiosemicarbazones show reduced toxicity in normal cells
Abstract
Three novel Cu(II) complexes with 3,4-dimethoxybenzylidene-substituted thiosemicarbazones were synthesized and evaluated for anticancer, antibacterial, and antioxidant activities. Our recent structure-activity relationship studies showed that Cu(II) complexes containing 3,4-dimethoxybenzylidene-substituted ligands can display potent anticancer activity, reaching single-digit IC 50 values, which prompted further investigation of this structural motif. The complexes examined here showed moderate antibacterial activity and distinct antioxidant profiles in the ABTS, DPPH, and ORAC-FL assays. Among them, the morpholine-containing complex Cu(dm-TSC-morph) 2 showed the most favorable anticancer selectivity, retaining low-micromolar activity against SK-MEL-28 and A-375 melanoma cells (IC 50 = 6.58 ± 0.71 and 9.20 ± 1.52 μM, respectively) while exhibiting lower toxicity toward BJ, HUVEC, and HEK-293 cells, with selectivity indices up to 4.88. Studies of mechanism of action revealed that Cu(dm-TSC-morph) 2 induced intracellular oxidative stress in melanoma cells. These findings identify the morpholine-containing derivative as the most promising compound in the analyzed series and support further development of selective Cu(II) thiosemicarbazone complexes.
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BibTeX
@misc{rogalewicz2026cuii,
title = {{Cu(II) complexes based on morpholine-substituted thiosemicarbazones show reduced toxicity in normal cells}},
author = {Bartłomiej Rogalewicz and Marcin Świątkowski and Magdalena Iwan and Joanna Kubik and Agnieszka Korga-Plewko and Monika Pitucha and Emil Borecki and Tomasz Boruta and Sylwia Ścieszka and Edyta Kordialik-Bogacka and Aleksandra Lis and Paweł Szymański and Anna Gajda and Agnieszka Czylkowska},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15009970/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009970/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Cu(II) complexes based on morpholine-substituted thiosemicarbazones show reduced toxicity in normal cells
AU - Bartłomiej Rogalewicz
AU - Marcin Świątkowski
AU - Magdalena Iwan
AU - Joanna Kubik
AU - Agnieszka Korga-Plewko
AU - Monika Pitucha
AU - Emil Borecki
AU - Tomasz Boruta
AU - Sylwia Ścieszka
AU - Edyta Kordialik-Bogacka
AU - Aleksandra Lis
AU - Paweł Szymański
AU - Anna Gajda
AU - Agnieszka Czylkowska
PY - 2026
DA - 2026/10/06
PB - ChemRxiv
DO - 10.26434/chemrxiv.15009970/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15009970/v1
AB - Three novel Cu(II) complexes with 3,4-dimethoxybenzylidene-substituted thiosemicarbazones were synthesized and evaluated for anticancer, antibacterial, and antioxidant activities. Our recent structure-activity relationship studies showed that Cu(II) complexes containing 3,4-dimethoxybenzylidene-substituted ligands can display potent anticancer activity, reaching single-digit IC 50 values, which prompted further investigation of this structural motif. The complexes examined here showed moderate antibacterial activity and distinct antioxidant profiles in the ABTS, DPPH, and ORAC-FL assays. Among them, the morpholine-containing complex Cu(dm-TSC-morph) 2 showed the most favorable anticancer selectivity, retaining low-micromolar activity against SK-MEL-28 and A-375 melanoma cells (IC 50 = 6.58 ± 0.71 and 9.20 ± 1.52 μM, respectively) while exhibiting lower toxicity toward BJ, HUVEC, and HEK-293 cells, with selectivity indices up to 4.88. Studies of mechanism of action revealed that Cu(dm-TSC-morph) 2 induced intracellular oxidative stress in melanoma cells. These findings identify the morpholine-containing derivative as the most promising compound in the analyzed series and support further development of selective Cu(II) thiosemicarbazone complexes.
ER -