Ruthenium(II)-mercapto Complexes with Anticancer Activity Interact with Topoisomerase IB
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Data
2020-03-01
Autores
da Silva, Monize M.
de Camargo, Mariana S.
Castelli, Silvia
de Grandis, Rone A. [UNESP]
Castellano, Eduardo E.
Deflon, Victor M.
Cominetti, Marcia R.
Desideri, Alessandro
Batista, Alzir A.
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Resumo
Herein we present four new ruthenium(II) complexes: [Ru(mtz)2(dppb)] (1), [Ru(mmi)2(dppb)] (2), [Ru(dmp)2(dppb)] (3), and [Ru(mpca)2(dppb)] (4), where mtz = 2-mercaptothiazoline; mmi = 2-mercapto-1-methyl-imidazole; dmp = 4,6-diamino-2 - m e r c a p t o p y r i m i d i n e; m p c a = 6 - m e r c a p t o p y r i d i n e - 3 - c a r b o x y l i c a c i d; dppb = 1,4-bis(diphenylphosphino)butane. In vitro cell culture experiments revealed cytotoxic activity for complexes 2, 3 and 4 against MCF-7 (breast, non-invasive), MDA-MB-231 (breast, invasive), A549 (lung), DU-145 (prostate) and HepG2 (liver) tumor cells, in some cases lower than the half maximal inhibitory concentration (IC50) for the reference drug (cisplatin). The deoxyribonucleic acid (DNA) interactions studied by viscosity measurements, gel electrophoresis and square-wave voltammetry indicated that the DNA binding affinity primarily occurs through non-covalent interactions. Only complex 2 was able to fully inhibit the DNA supercoiled relaxation mediated by human topoisomerase IB (Top IB). The analysis indicates that complex 2 inhibits the cleavage and the reconnection steps of the catalytic cycle, being both a poison and a catalytic inhibitor.
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Palavras-chave
Cytotoxicity, Mercapto ligands, Ruthenium(II) complexes, Topoisomerase IB
Como citar
Journal of the Brazilian Chemical Society, v. 31, n. 3, p. 536-549, 2020.