Cu(II) complexes based on morpholine-substituted thiosemicarbazones show reduced toxicity in normal cells
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7220740438