Palladium (II) complexes as inhibitors of cathepsin B and topoisomerase I beta: Synthesis, characterization, and cytotoxicity

被引：4

作者：

Akinyemi, Amos O. ^{[1
,3
]}

Pereira, George B. S. ^{[1
]}

Oliveira, Gabriela P. ^{[1
]}

Lima, Mauro A. ^{[1
]}

Rocha, Josias S. ^{[1
]}

Costa, Vinicius A. ^{[1
]}

Fortaleza, Dario B. ^{[1
]}

Teixeira, Tamara ^{[1
]}

Zanotti, Karine ^{[1
]}

Forim, Moacir Rossi ^{[1
]}

Araujo-Neto, Joao H. ^{[2
]}

Ellena, Javier ^{[2
]}

Rocha, Fillipe Vieira ^{[1
]}

机构：

[1] Univ Fed Sao Carlos, Dept Chem, BR-13565905 Sao Carlos, SP, Brazil

[2] Univ Sao Paulo, Sao Carlos Inst Phys, BR-13566590 Sao Carlos, SP, Brazil

[3] Univ Kentucky, Dept Toxicol & Canc Biol, Lexington, KY USA

来源：

JOURNAL OF MOLECULAR STRUCTURE | 2023年 / 1294卷

基金：

巴西圣保罗研究基金会;

关键词：

Palladium (II); Cathepsin B; Topoisomerase; Cytotoxicity; DNA interactions; HETEROCYCLIC CARBENE COMPLEXES; BREAST-CANCER CELLS; DNA-BINDING; PLATINUM(II) COMPLEXES; MOLECULAR DOCKING; LIGAND; THIOSEMICARBAZONES; CATALYST;

D O I：

10.1016/j.molstruc.2023.136460

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

This research presents the synthesis, characterization, anticancer activity, and investigation of biological targets of three new palladium (II) complexes. The compounds were characterized by spectroscopies techniques (UV-Vis, NMR, and IR), elemental analysis, mass spectrometry, and one for monocrystal X-ray diffraction. The cytotoxic activity of the complexes against two cell lines, A2780cis (cisplatin resistance ovarian tumor cell line) and MRC-5 (non-tumor lung cell), was evaluated. The in vitro cytotoxicity assays using the MTT method revealed a significant cytotoxic activity of the palladium complexes against the evaluated cell lines, highlighting the resistance tumor cell line, A2780cis. Also, DNA interaction studies suggested that the compounds either do not interact, or interact weakly with DNA via groove and/or electrostatically. The interaction assay demonstrated that the compounds can weakly to moderately bind to the HSA biomolecule through electrostatic or van der Waals forces. In addition, agarose gel electrophoresis assays indicated that the complexes could not inhibit the action of the enzyme, topoisomerase II alpha. Nonetheless, the complexes demonstrated a promising target against topoisomerase I beta by promoting its inhibition. Finally, fluorescence studies revealed the capacity of irreversible inhibition of the complexes against the enzyme, cathepsin B. 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) antioxidant assay did not show significant scavenging of DPPH radical. The results showed that the proposed structural features generate compounds of high cytotoxicity that can inhibit the action of cathepsin B and topoisomerase I beta.

引用

页数：14

共 70 条

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