Anticancer activity and DNA interaction of ruthenium acetate clusters bearing azanaphthalene ancillary ligands

Author(s)

Possato, Bruna ^[1] ; Hauch Chrispim, Pedro Branco ^[1] ; Alves, Jacqueline Querino ^[1] ; Barbosa Ramos, Loyanne Carla ^[2] ; Marques, Elise ^[3] ; de Oliveira, Arthur Cavalcante ^[1] ; da Silva, Roberto Santana ^[2] ; Barboza Formiga, Andre Luiz ^[4] ; Nikolaou, Sofia ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Lab Atividade Biol & Quim Supramol Compostos Coor, Dept Quim, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto, Av Do Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[3] Inst Fed Educ Ciencia & Tecnol Rondonia IFRO, BR-76900793 Ji Parana, RO - Brazil

^[4] Univ Estadual Campinas, Inst Quim, POB 6154, BR-13083970 Campinas, SP - Brazil

• Document type: Journal article
• Source: Polyhedron; v. 176, JAN 15 2020.
• Web of Science Citations: 3

Abstract

Six triruthenium complexes (1-6) ({[}Ru3O(CH3COO)(6)(L)(3)]PF6, L = quinazoline (qui) (complex 1), 5-nitroisoquinoline (5-nitroiq) (complex 2), 5-bromoisoquinoline (5-brig) (complex 3), isoquinoline (iq) (complex 4), 5-aminoisoquinoline (5-amiq) (complex 5), and 5,6,7,8-tetrahydroisoquinoline (thiq) (complex 6)) have been studied regarding their anti-cancer activity (B16F10 and A549 cells) and their interactions with fish sperm DNA (fs-DNA). The crystallographic data of complex 4 show the typical triangular geometry, where the three isoquinoline ligands display different degrees of co-planarity with the {[}Ru3O] unit. In the range of 2 to 200 mu M, these complexes make B16F10 cells less viable. The overall cytotoxicity order is complex 4 > complex 6 > complex 2 > complex 5 > complex 1. The two first complexes have IC50 of 10 and 50 mu M, respectively, being less toxic to L929 non-tumoral cells. The complexes can displace ethidium bromide (EB) from DNA, but the intercalation constant values (K-app similar to 10(5) M-1) are low due to the smaller size of the azanaphtalene ligands as compared to classic intercalating molecules. Complex 5 provides the highest constants in both the EB displacement (K-app = 12.5 x 10(5) M-1) and direct spectrophotometric titration with fs-DNA (K-b = 6.3 x 10(4) M-1) assays, possibly because its amino group can assist interaction with DNA through hydrogen bonds. Hypochromism of complexes IC band was observed (T = 310 K), suggesting hydrophobic contributions. Low values of K-app and circular dichroism spectra for DNA-compound 6 mixtures, suggest semi-intercalative and major groove binding interaction modes. Compared to cisplatin, incubation of complexes 1-6 with plasmid pUC19 shows no DNA cleavage. Results for the interaction with DNA do not correlate with cytotoxicity, which suggests that DNA is not the pharmacological target of this class of compounds. (C) 2019 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 18/18060-3 - Use of inorganic supramolecular structures for the development of functional molecules and controlled release of bioactive species
• Grantee: Sofia Nikolaou
• Support Opportunities: Regular Research Grants
• FAPESP's process: 14/50906-9 - INCT 2014: in Functional Complex Materials
• Grantee: Fernando Galembeck
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 15/20302-7 - Using non-steroidal antiinflammatory drugs, azanaphtalenes and phenazines as ligands for the development of bi- and trinuclear rutenium carboxylates with potential antialergic, tumoricide and tripanocide activities
• Grantee: Sofia Nikolaou
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/22127-2 - Development of novel materials strategic for integrated analytical devices
• Grantee: Lauro Tatsuo Kubota
• Support Opportunities: Research Projects - Thematic Grants