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© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Two new complexes of Ru(II) with mixed ligands were prepared: [Ru(bpy)2smp](PF6) (1) and [Ru(phen)2smp](PF6) (2), in which smp = sulfamethoxypyridazine; bpy = 2,2′-bipyridine; phen = 1,10-phenanthroline. The complexes have been characterized by elemental and conductivity analyses; infrared, NMR, and electrospray ionization mass spectroscopies; and X-ray diffraction of single crystal. Structural analyses reveal a distorted octahedral geometry around Ru(II) that is bound to two bpy (in 1) or two phen (in 2) via their two heterocyclic nitrogens and to two nitrogen atoms from sulfamethoxypyridazine—one of the methoxypyridazine ring and the sulfonamidic nitrogen, which is deprotonated. Both complexes inhibit the growth of chronic myelogenous leukemia cells. The interaction of the complexes with bovine serum albumin and DNA is described. DNA footprinting using an oligonucleotide as substrate showed the complexes’ preference for thymine base rich sites. It is worth notifying that the complexes interact with the Src homology SH3 domain of the Abl tyrosine kinase protein. Abl protein is involved in signal transduction and implicated in the development of chronic myelogenous leukemia. Nuclear magnetic resonance (NMR) studies of the interaction of complex 2 with the Abl-SH3 domain showed that the most affected residues were T79, G97, W99, and Y115.

Details

Title
New Heteroleptic Ruthenium(II) Complexes with Sulfamethoxypyridazine and Diimines as Potential Antitumor Agents
Author
Ariane CC de Melo 1 ; Santana, Jaime MSVP 1 ; Kelen JRC Nunes 1 ; Rodrigues, Bernardo L 1 ; Castilho, Nathalia 2 ; Philipe Gabriel 2 ; Moraes, Adolfo H 1   VIAFID ORCID Logo  ; de A Marques, Mayra 3   VIAFID ORCID Logo  ; Guilherme AP de Oliveira 3   VIAFID ORCID Logo  ; de Souza, Ívina P 4 ; Terenzi, Hernán 2 ; Pereira-Maia, Elene C 1   VIAFID ORCID Logo 

 Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil 
 Department of Biochemistry, Universidade Federal de Santa Catarina, Florianópolis 88040900, SC, Brazil 
 Programa de Biologia Estrutural, Instituto de Bioquímica Médica Leopoldo de Meis, Instituto Nacional de Biologia Estrutural e Bioimagem, Centro Nacional de Ressonância Magnética Nuclear Jiri Jonas, Universidade Federal do Rio de Janeiro, Rio de Janeiro 21941590, RJ, Brazil 
 Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil; Department of Chemistry, Centro Federal de Educação Tecnológica de Minas Gerais, Belo Horizonte 30421-169, MG, Brazil 
First page
2154
Publication year
2019
Publication date
2019
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2549089696
Copyright
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.