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Open AccessArticle

New Heteroleptic Ruthenium(II) Complexes with Sulfamethoxypyridazine and Diimines as Potential Antitumor Agents

1
Department of Chemistry, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil
2
Department of Biochemistry, Universidade Federal de Santa Catarina, Florianópolis 88040900, SC, Brazil
3
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
4
Department of Chemistry, Centro Federal de Educação Tecnológica de Minas Gerais, Belo Horizonte 30421-169, MG, Brazil
*
Author to whom correspondence should be addressed.
Academic Editor: Iztok Turel
Molecules 2019, 24(11), 2154; https://doi.org/10.3390/molecules24112154
Received: 8 May 2019 / Revised: 30 May 2019 / Accepted: 1 June 2019 / Published: 7 June 2019
(This article belongs to the Special Issue Medicinal Importance of Ruthenium Compounds)
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. View Full-Text
Keywords: ruthenium complexes; sulfonamide; Abl tyrosine kinase; bovine serum albumin; DNA ruthenium complexes; sulfonamide; Abl tyrosine kinase; bovine serum albumin; DNA
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de Melo, A.C.; Santana, J.M.; Nunes, K.J.; Rodrigues, B.L.; Castilho, N.; Gabriel, P.; Moraes, A.H.; Marques, M.A.; de Oliveira, G.A.; de Souza, Í.P.; Terenzi, H.; Pereira-Maia, E.C. New Heteroleptic Ruthenium(II) Complexes with Sulfamethoxypyridazine and Diimines as Potential Antitumor Agents. Molecules 2019, 24, 2154.

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