49773-66-2Relevant academic research and scientific papers
Influence of complexation of thiosemicarbazone derivatives with Cu (II) ions on their antitumor activity against melanoma cells
Pitucha, Monika,Korga-Plewko, Agnieszka,Czylkowska, Agnieszka,Rogalewicz, Bart?omiej,Drozd, Monika,Iwan, Magdalena,Kubik, Joanna,Humeniuk, Ewelina,Adamczuk, Grzegorz,Karczmarzyk, Zbigniew,Fornal, Emilia,Wysocki, Waldemar,Bartnik, Paulina
, p. 1 - 25 (2021)
A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.
A thiosemicarbazone derivative induces triple negative breast cancer cell apoptosis: possible role of miRNA-125a-5p and miRNA-181a-5p
El Majzoub, Rania,Fayyad-kazan, Mohammad,Nasr El Dine, Assaad,Makki, Rawan,Hamade, Eva,Grée, René,Hachem, Ali,Talhouk, Rabih,Fayyad-Kazan, Hussein,Badran, Bassam
, p. 1431 - 1443 (2019/11/03)
Background: Breast cancer, the most commonly diagnosed malignancy in women, accounts for the highest cancer-related deaths worldwide. Triple negative breast cancer (TNBC), lacking the expression of estrogen, progesterone and HER2 receptors, has an aggressive clinical phenotype and is susceptible to chemotherapy but not to hormonal or targeted immunotherapy. In an attempt to identify potent and selective anti-TNBC agents, a set of thiosemicarbazone derivatives were screened for their cytotoxic activity against MDA-MB 231 breast cancer cell line. Methods: MTT assay was used to examine cell viability. P53 phosphorylation status, poly (ADP-ribose) polymerase (PARP) cleavage as well as Bcl2 and Bax protein levels were assessed by Western blot. Quantitative Real Time-PCR was carried out to characterize miRNAs expression levels. Results: Combining Cisplatin + thiosemicarbazone compound 4 showed potent anti-TNBC potential. Cisplatin + compound 4 significantly enhanced p53 phosphorylation, induced Bax amount, reduced Bcl2 protein levels, enhanced PARP cleavage and modulated miRNAs expression profile in TNBCs, with a particular overexpression of miR-125a-5p and miR-181a-5p. Intriguingly, miR-125a-5p and miR-181a-5p could significantly downregulate BCL2 expression by binding to their target sites in the 3′UTR. Conclusions: Collectively, our results demonstrate an anti-TNBC activity of Cisplatin + thiosemicarbazone compound 4 combination mediated via induction of apoptosis.
