A novel water-soluble thiosemicarbazone Schiff base ligand and its complexes as potential anticancer agents and cellular fluorescence imaging

• Published in: Journal of biological inorganic chemistry Vol. 28; no. 5; pp. 457 - 472
• Main Authors: Feizpour, Sima, Hosseini-Yazdi, Seyed Abolfazl, Safarzadeh, Elham, Baradaran, Behzad, Dusek, Michal, Poupon, Morgane
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01-08-2023; Springer Nature B.V
• Subjects: Adenocarcinoma; Antitumor agents; Apoptosis; Biochemistry; Biomedical and Life Sciences; Cancer; Cell cycle; Cell death; Copper; Crystal structure; Crystallography; Fibroblasts; Flow cytometry; Fluorescence microscopy; Inorganic chemistry; Life Sciences; Ligands; Manganese; Microbiology; Original Paper; Paclitaxel; Sarcoma; X-ray crystallography; X-ray crystallography; Flow cytometry; Cytotoxicity; Anticancer activity; Cell cycle; Apoptosis
• ISSN: 1432-1327; 0949-8257; 1432-1327
• DOI: 10.1007/s00775-023-02001-5

A novel fluorescent ligand (H
2
LCl⋅1.5CH
3
OH,
1
) was synthesized and metal complexes of
1
with Mn(II), Fe(III), Ni(II), Cu(II), and Zn(II) were obtained as Mn(HL)
2
Cl
2
(
2
), Fe(HL)
2
Cl
3
⋅3H
2
O (
3
), Ni(L)(HL)Cl⋅8H
2
O (
4
), Cu(HL)Cl
2
⋅4H
2
O (
5
), Zn(H
2
L)Cl
3
(
6
), respectively. These compounds were identified by spectroscopic methods, elemental analysis, molar conductivity, and single-crystal X-ray crystallography. According to the crystal structure of
4
nickel (II), center is surrounded by two ligands in a distorted octahedral geometry. The ligand and its complexes are soluble in water and have excellent stability. In vitro anti-proliferative activity of these compounds was evaluated against human breast adenocarcinoma (MCF-7) and human lipo-sarcoma (SW-872) as cancer cells and human fibroblasts (HFF-2) as normal cells by MTT assay. Interestingly, complex
5
exhibited excellent activity against both cancer cells with low IC
50
value 22.18 ± 0.35 μg/mL (35.66 ± 0.56 μM) for SW-872 and 79.41 ± 3.54 μg/mL (127.6 ± 5.69 μM) for MCF-7 among the compounds and in comparison with paclitaxel (PTX) which acts finely. Morphological changes were evaluated by flow cytometry that revealed apoptosis is the main cause of cell death. Likewise, cell cycle studies indicated the cell cycle arrest in the G
1
and S phases for complex
5
against MCF-7 and SW-872 cancer cells, while complex
6
could arrest the MCF-7 and SW-872 cells in G
2
and G
1
phases, respectively. All of the compounds are fluorescent which enabled us to monitor the uptake and intracellular distribution in living human cancer cells by fluorescence microscopy.
Graphical abstract