Journal
JOURNAL OF MOLECULAR STRUCTURE
Volume 1191, Issue -, Pages 118-128Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.molstruc.2019.04.119
Keywords
Imidazolium motifs; Pd(II) saldach; Cytotoxicity; CT-DNA interaction-HER2/neu; Apoptosis
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The HER2/neu has shown a potential role in the choice of active chemotherapy for breast tumors because of its prognostic relevance and putative role in predicting drug resistance. Moreover, suppressing DNA replication has become an attractive strategy for treating cancer patients. In this attempt, the present study aimed to prepare new series of bis-imidazolium-based saldach {H-2(Et)(2) saldach (Bu-n-Im(+)-X-)(2)} and their cis-Pd(II) complexes (saldach = N,N'-bis-(salicylidene)-R,R-1,2-diaminocyclohexane; X =Cl, PF6, BF4) as anticancer agents. The in vitro cytotoxicity activity of new cis-Pd(II) complexes against human breast adenocarcinoma cell lines (MCF-7) revealed higher growth-inhibitory effect than the native ligands. They induced a significant decrease for the protein HER2/neu expression with p <0.05 and tumor necrosis factor (TNF-alpha) (p <0.05), while the tumor suppressor protein P53 was expressed in a highly significant upregulation p <0.01. Moreover, complex 5a was the most potent active compound (IC50 = 8.5 +/- 0.2 mu M) in inhibition of cell proliferation. Additionally, in vitro studies of Pd(II) complex (5a) using UV-Vis spectroscopy and binding affinity toward the calf thymus (CT) DNA) showed a combination of covalent, intercalation, hydrogen bonding interactions through formation of (CT-DNA). (C) 2019 Elsevier B.V. All rights reserved.
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