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

• Published in: Molecules (Basel, Switzerland) Vol. 24; no. 11; p. 2154
• Main Authors: de Melo, Ariane C C, Santana, Jaime M S V P, Nunes, Kelen J R C, Rodrigues, Bernardo L, Castilho, Nathalia, Gabriel, Philipe, Moraes, Adolfo H, Marques, Mayra de A, de Oliveira, Guilherme A P, de Souza, Ívina P, Terenzi, Hernán, Pereira-Maia, Elene C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 07.06.2019; MDPI
• Subjects: Abl protein; Abl tyrosine kinase; Antibiotics; Apoptosis; Bovine serum albumin; Cancer; Chronic myeloid leukemia; Crystal structure; Cytotoxicity; Deoxyribonucleic acid; DNA; Domains; Footprinting; Homology; Hydrogen bonds; Infrared analysis; Ionization; Leukemia; Ligands; Myeloid leukemia; Nitrogen; Nitrogen atoms; NMR; Nuclear magnetic resonance; Protein-tyrosine kinase; Proteins; Ruthenium; ruthenium complexes; Ruthenium compounds; Serum albumin; Signal transduction; Single crystals; Sulfamethoxypyridazine; sulfonamide; Thymine; Tyrosine; X-ray diffraction; Abl tyrosine kinase; sulfonamide; DNA; bovine serum albumin; ruthenium complexes
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules24112154

Two new complexes of Ru(II) with mixed ligands were prepared: [Ru(bpy) smp](PF ) ( ) and [Ru(phen) smp](PF ) ( ), 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 ) or two phen (in ) 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 with the Abl-SH3 domain showed that the most affected residues were T79, G97, W99, and Y115.