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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Computational studies, design and synthesis of Pd(II)-based complexes: Allosteric inhibitors of the Human Topoisomerase-II alpha

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Rocha, Fillipe V. [1] ; Farias, Renan L. [2] ; Lima, Mauro A. [1] ; Batista, Victor S. [3] ; Nascimento-Junior, Nailton M. [3] ; Garrido, Saulo S. [4] ; Leopoldino, Andrea M. [5] ; Goto, Renata N. [5] ; Oliveira, Adriano B. [6] ; Beck, Johannes [7] ; Landvogt, Christian [7] ; Mauro, Antonio E. [2] ; Netto, Adelino V. G. [2]
Total Authors: 13
[1] UFSCar Univ Fed Sao Carlos, Dept Quim, Sao Carlos, SP - Brazil
[2] UNESP Univ Estadual Paulista, Inst Quim, Dept Quim Geral & Inorgan, Araraquara - Brazil
[3] UNESP Univ Estadual Paulista, Inst Quim, Dept Quim Organ, Araraquara - Brazil
[4] UNESP Univ Estadual Paulista, Inst Quim, Dept Bioquim & Tecnol Quim, Araraquara - Brazil
[5] Univ Sao Paulo, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil
[6] Univ Fed Sergipe, Dept Quim, Sao Cristovao - Brazil
[7] Rheinische Friedrich Wilhelms Univ Bonn, Inst Anorgan Chem, Bonn - Germany
Total Affiliations: 7
Document type: Journal article
Source: Journal of Inorganic Biochemistry; v. 199, OCT 2019.
Web of Science Citations: 7

Herein, a robust docking protocol was developed by using a low-cost workflow to highlight the modulation at ATPase domain from Human Topoisomerase-Ha (TOP2A) towards four novel Pd(II)-complexes bearing N,S-donor ligands. In vitro TOP2A inhibition assay confirmed the ability of them to prevent the enzyme functions into concentration ranging at 6.25-25 mu M. These results exhibited more effectivity than anticancer agent etoposide (35 mu M) and merbarone (40-50 mu M). The compounds were screened via Resazurin assay against MCF-7, MDA-MB-231 (Human breast), DU-145 (Human prostate), A549 (Human lung) and Ca127 (Human tongue) tumor cell lines revealing great cytotoxic effects, primarily to MCF-7 (IC50 = 1.81-4.46 mu M). As well, 1-4 exhibited their selectivity index (SI) higher than cisplatin against HEK-293 (human kidney) normal cells, at least 11.6-fold = (SI1.4 = 1.4-5.0; Sl(cis) = 0.12). Further, Red Blood Cell hemolytic test suggested in vitro non-toxic character for compound 4, previously evaluated as the most effective TOP2A inhibitor. (AU)

FAPESP's process: 16/04201-9 - Transition metal compounds bearinhg thiosemicarbazones and phosphines as ligand: investigation of cytotoxicity and mechanism of action
Grantee:Fillipe Vieira Rocha
Support type: Regular Research Grants
Grantee:Adelino Vieira de Godoy Netto
Support type: Regular Research Grants
FAPESP's process: 13/20156-5 - Design of new thiosemicarbazones and their Cu(II) and Pd(II) complexes as topoisomerase inhibitors
Grantee:Fillipe Vieira Rocha
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 12/15486-3 - Pd(II) compounds: synthesis, cytotoxicity, and DNA binding studies
Grantee:Regina Celia Galvao Frem
Support type: Regular Research Grants