Your browser doesn't support javascript.
loading
Mononuclear η6-arene ruthenium(II) complexes with pyrazolyl-pyridazine ligands: synthesis, CT-DNA binding, reactivity towards glutathione, and cytotoxicity.
Kanyora, Amos K; Omondi, Reinner O; Ongoma, Peter; Omolo, Josiah O; Welsh, Athi; Prince, Sharon; Gichumbi, Joel; Mambanda, Allen; Smith, Gregory S.
Afiliación
  • Kanyora AK; Department of Chemistry, Egerton University, P.O Box 536-20115, Egerton, Kenya. kimem.aka12@gmail.com.
  • Omondi RO; Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
  • Ongoma P; Department of Chemistry, Egerton University, P.O Box 536-20115, Egerton, Kenya.
  • Omolo JO; Department of Chemistry, Egerton University, P.O Box 536-20115, Egerton, Kenya.
  • Welsh A; Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
  • Prince S; Department of Human Biology, Faculty of Health Science, Observatory, University of Cape Town, Cape Town, 7925, South Africa.
  • Gichumbi J; Department of Physical Sciences, Chuka University, P.O. Box 109-60400, Chuka, Kenya.
  • Mambanda A; School of Chemistry and Physics, University of KwaZulu-Natal, Private Bag X01, Scottsville, Pietermaritzburg, 3209, South Africa.
  • Smith GS; Department of Chemistry, University of Cape Town, Rondebosch, 7701, South Africa.
J Biol Inorg Chem ; 29(2): 251-264, 2024 03.
Article en En | MEDLINE | ID: mdl-38494554
ABSTRACT
Organometallic η6-arene ruthenium(II) complexes with 3-chloro-6-(1H-pyrazol-1-yl)pyridazine (Ru1, Ru2, and Ru5) and 3-chloro-6-(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine (Ru3-4) N,N' heterocyclic and η6-arene (cymene (Ru1-4) or toluene (Ru 5)) have been synthesized. The ruthenium(II) complexes have common "three-legged piano-stool" pseudo-octahedral structures known for half-sandwich complexes. Evolution of their UV-Visible absorption spectra in PBS buffer or DMSO over 24 h confirmed their good solvolysis stability. Titrations of the complexes with the calf thymus DNA (CT-DNA) were monitored using UV-Visible absorption and fluorescence spectroscopies. The complexes interact moderately with CT-DNA and their binding constants are in the order of 104 M-1. Competitive binding of the complexes to a DNA-Hoechst 33,258 depicted competitive displacement of Hoechst from DNA's minor grooves. These complexes bind to glutathione forming GSH-adducts through S coordination by replacement of a halide, with the iodo-analogues having higher binding constants than the chloro-complexes. Cyclic voltammograms of the complexes exhibited one electron-transfer quasi-reversible process. Trends in the molecular docking data of Ru1-5/DNA were similar to those for DNA binding constants. Of the five, only Ru1, Ru3 and Ru5 showed some activity (moderate) against the MCF-7 breast cancer cells with IC50 values in the range of 59.2-39.9 for which Ru5 was the most active. However, the more difficult-to-treat cell line, MDA-MB 231 cell was recalcitrant to the treatment by these complexes.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Rutenio / ADN / Complejos de Coordinación / Glutatión / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: J Biol Inorg Chem Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Kenia

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Rutenio / ADN / Complejos de Coordinación / Glutatión / Antineoplásicos Límite: Animals / Humans Idioma: En Revista: J Biol Inorg Chem Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Kenia