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Novel Isatin-based activator of p53 transcriptional functions in tumor cells

Journal: Molecular Biology Research Communications (Vol.8, No. 3)

Publication Date:

Authors : ; ; ; ; ; ; ; ;

Page : 119-128

Keywords : p53; Transcriptional activity; Isatin-Schiff base; Metal complex; Tumor cells;

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Abstract

Bioinorganic medicinal chemistry remains a hot field for research aimed at developing novel anti-cancer treatments. Discovery of metal complexes as potent antitumor chemotherapeutics such as cisplatin led to a significant shift of focus toward organometallic/ bioinorganic compounds containing transition metals and their chelates as novel scaffolds for drug discovery. In that way, transition metal complexes coordinated to essential biological scaffolds represent a highly promising class of compounds for design of novel target-specific therapeutics. Here, we report novel data on p53 activating Isatin-based Cu(II) complex exhibiting cytotoxic properties towards HCT116 and MCF7 tumor cell lines, as confirmed by cell viability assay and flow cytometry analysis of apoptosis. Furthermore, putative p53-mediated mechanism of action of this compound is supported by quantitative analysis of TP53, MDM2 and PUMA genes expression, as well as luciferase-based p53 pathway activation assay. Multiplex immunoassay analysis of inflammatory markers revealed potential modulation of several cytokines and chemokines.

Last modified: 2019-10-07 16:54:21