Novos complexos de Rutênio(II) contendo Metronidazol: investigação citotóxica e estudo da interação com o DNA

Abstract

Four novel ruthenium(II) complexes containing ligands mono and bidentate were obtained: [RuCl(MTNZ)(dppb)(4,4’-Mebipy)]PF 6 , [RuCl(MTNZ)(dppb)(4,4’- Methoxybipy)]PF 6 , [RuCl(MTNZ)(dppb)(bipy)]PF 6 and [RuCl(MTNZ)(dppb) (phen)]PF 6 , where, MTNZ = metronidazole, dppb = 1,4- Bis(diphenylphosphino)butane, 4,4’-Mebipy = 4,4’-dimethyl-2,2’-bipyridine, 4,4’- Methoxybipy = 4,4’-dimethoxy-2,2’-bipyridine, bipy = 2,2’-bipyridine and phen = 1,10- phenanthroline. The complexes were characterized by elemental analysis, molar conductivity, infrared and UV-Vis spectroscopy, 31 P{ 1 H}, 1 H, 13 C{ 1 H} and Dept 135 NMR and cyclic voltammetry. The interactions of complexes with DNA were evaluated, and the cytotoxicity profiles of compounds were determined using four different tumor cell lines derived from human cancers (melanoma: SK-MEL-147, liver: Hep G2, breast: MCF-7, and lung: A549). Higher cytotoxic activity was observed for compounds [RuCl(MTNZ)(dppb)(4,4’-Mebipy)]PF 6 and [RuCl(MTNZ)(dppb)(bipy)]PF 6 against cell breast cancer (MCF-7), with IC 50 17,47 ± 1,14 (SI 2,7) and IC 50 16,88 ±

0,97 (SI 2,9), respectively. Furthermore, annexin V assays showed that [RuCl(MTNZ)(dppb)(4,4'-Mebipy)]PF6 and [RuCl(MTNZ)(dppb)(bipy)]PF6 can induce apoptosis in MCF cells -7 and cell cycle progression analysis showed that they alter the cell cycle progression dynamics and cause cycle blocking in the G1/S transition. In summary, the data obtained in the present study support further investigations into molecular targets of the [RuCl(MTNZ)(dppb)(4,4'-Mebipy)]PF6 and [RuCl(MTNZ)(dppb)(bipy)]PF6 complexes for potential application against the MCF-7 breast cancer lineage.