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Evaluation of anticancer activity of novel platinum(II) bis(thiosemicarbazone) complex against breast cancer.
- Source :
-
Bioorganic chemistry [Bioorg Chem] 2024 Jul; Vol. 148, pp. 107486. Date of Electronic Publication: 2024 May 22. - Publication Year :
- 2024
-
Abstract
- The study aims to synthesize a novel bis(thiosemicarbazone) derivative based on platinum (thioPt) and evaluate its anticancer properties against MFC-7 and MDA-MB-231 breast cancer cells. A new platinum complex was synthesised by reacting K <subscript>2</subscript> PtCl <subscript>4</subscript> with 2,2'-(1,2-diphenylethane-1,2-diylidene)bis(hydrazine-1-carbothioamide) in ethanol in the presence of K <subscript>2</subscript> CO <subscript>3</subscript> . In the obtained complex, the platinum atom is coordinated by a conjugated system = N-NC-S-The structures of the new compound were characterised using NMR spectroscopy, HR MS, IR, and X-ray structural analysis. The obtained results of the cytotoxicity assay indicate that compound thioPt had potent anticancer activity (MCF-7: 61.03 ± 3.57 µM, MDA-MB-231: 60.05 ± 5.40 µM) with less toxicity against normal MCF-10A breast epithelial cells, even compared to the reference compound (cisplatin). In addition, subsequent experiments found that thioPt induces apoptosis through both an extrinsic (↑caspase 8 activity) and intrinsic (↓ΔΨ <subscript>m</subscript> ) pathway, which ultimately leads to an increase in active caspase 3/7 levels. The induction of autophagy and levels of proteins involved in this process (LC3A/B and Beclin-1) were examined in MCF-7 and MDA-MB-231 breast cancer cells exposed to tested compounds (thio, thioPt, cisPt) at a concentration of 50 µM for 24 h. Based on these results, it can be concluded that thio and thioPt do not significantly affect the autophagy process. This demonstrates their superiority over cisplatin, which can stimulate cancer cell survival through its effect on stimulation of autophagy.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Humans
Structure-Activity Relationship
Molecular Structure
Female
Dose-Response Relationship, Drug
Cell Line, Tumor
Organoplatinum Compounds pharmacology
Organoplatinum Compounds chemistry
Organoplatinum Compounds chemical synthesis
Coordination Complexes pharmacology
Coordination Complexes chemistry
Coordination Complexes chemical synthesis
Platinum chemistry
Platinum pharmacology
Autophagy drug effects
Antineoplastic Agents pharmacology
Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Thiosemicarbazones pharmacology
Thiosemicarbazones chemistry
Thiosemicarbazones chemical synthesis
Drug Screening Assays, Antitumor
Breast Neoplasms drug therapy
Breast Neoplasms pathology
Apoptosis drug effects
Cell Proliferation drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1090-2120
- Volume :
- 148
- Database :
- MEDLINE
- Journal :
- Bioorganic chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 38788367
- Full Text :
- https://doi.org/10.1016/j.bioorg.2024.107486