1. New Heteroleptic Ruthenium(II) Complexes with Sulfamethoxypyridazine and Diimines as Potential Antitumor Agents.
- Author
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de Melo ACC, Santana JMSVP, Nunes KJRC, Rodrigues BL, Castilho N, Gabriel P, Moraes AH, Marques MA, de Oliveira GAP, de Souza ÍP, Terenzi H, and Pereira-Maia EC
- Subjects
- Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Circular Dichroism, Humans, K562 Cells, Leukemia, Myelogenous, Chronic, BCR-ABL Positive drug therapy, Molecular Structure, Organometallic Compounds chemistry, Organometallic Compounds pharmacology, Proto-Oncogene Proteins c-abl chemistry, Proto-Oncogene Proteins c-abl metabolism, Spectrometry, Mass, Electrospray Ionization, X-Ray Diffraction, src Homology Domains, Antineoplastic Agents chemical synthesis, Leukemia, Myelogenous, Chronic, BCR-ABL Positive metabolism, Organometallic Compounds chemical synthesis, Ruthenium chemistry, Sulfamethoxypyridazine chemistry
- Abstract
Two new complexes of Ru(II) with mixed ligands were prepared: [Ru(bpy)
2 smp](PF6 ) ( 1 ) and [Ru(phen)2 smp](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.- Published
- 2019
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