In vitro cytotoxicity and in vivo zebrafish toxicity evaluation of Ru(ii)/2-mercaptopyrimidine complexes

Abstract

Ru(ii)/2-mercaptopyrimidine complexes active against cancer cells did not present toxic effects during embryonic and larval development of zebrafish.

Ruthenium(II) Diphosphine Complexes with Mercapto Ligands That Inhibit Topoisomerase IB and Suppress Tumor Growth In Vivo

“…Compared to the Ru–P bond distances (Table S1), the bond lengths involving the axial P atoms (P1 and P4) were slightly longer than those involving the equatorial P atoms (P2 and P3), which could be related to a competitive effect due to the trans influence between the P atoms, causing the Ru–P bond to elongate along the axial position. The geometric parameters (bond lengths, bond angles, and torsional angles) obtained for complexes Ru1 – Ru5 were consistent with the expected values for related ruthenium­(II) complexes bearing N,S-donor ligands. , …”

“…The geometric parameters (bond lengths, bond angles, and torsional angles) obtained for complexes Ru1−Ru5 were consistent with the expected values for related ruthenium(II) complexes bearing N,S-donor ligands. 20,38 In the region 3200−3100 cm −1 of the IR spectra of complexes Ru1−Ru5, the absence of a broad band confirms the monoanionic coordination of the mercapto ligands to ruthenium. The spectra of the free mercapto ligands are characterized by the presence of a broad band referring to the ν(N−H) mode.…”

“…Within this theme, we had previously designed, synthesized, and studied the chemistry, reactivity, and cytotoxic properties of ruthenium­(II) phosphine complexes bearing mercapto ligands (N-S). − Herein, we will focus on the cytotoxicity of these complexes and their interaction with biological molecules, mainly DNA , and proteins, , to get information about their mechanism of action and to try to shed some light on possible structure–activity relationships in these systems. Remarkably, complexes with the general formulas [Ru­(N-S)­(bipy)­(dppb)]­PF 6 and [Ru­(N-S)­(bipy)­(PPh 3 ) 2 ]­PF 6 [where bipy = 2,2′-bipyridine, dppb = 1,4-bis­(diphenylphosphino)­butane, and PPh 3 = triphenylphosphine] exert promising cytotoxic activity against different cancer cell lines in vitro. , The most active complexes of these series have IC 50 values ranging from 10 to 0.05 μM, especially against the human lung (A549) and breast (MDA-MB-231) cancer cell lines.…”

Ruthenium(II) Phosphine/Mercapto Complexes: Their in Vitro Cytotoxicity Evaluation and Actions as Inhibitors of Topoisomerase and Proteasome Acting as Possible Triggers of Cell Death Induction

“…The Ru−N2 and Ru−S1 bond distances are in the ranges of 2.16−2.25 and 2.39−2.43 Å, respectively, and are in the normal ranges for such ruthenium(II) compounds. 22,26,32 The mercapto ligands, coordinated to the metal, are negatively charged with electron delocalization on S2 In the structures, the dphppy ligand is coordinated to the ruthenium metal in a P,N-chelating mode, forming a fourmembered chelate ring with a bite angle in the range of 67.0− 67.5°. The pyridyl ring provides limited flexibility to the ligand, where the phosphorus atom is pulled "off-axis" toward the pyridine nitrogen atom.…”

Zebrafish as an Emerging Model System in the Global South: Two Decades of Research in Brazil

“…80 Moreover, in the last few years, many transgenic, knockdown and mutant lineages have been created for pharmacological studies. 77,80 In Brazil, the zebrafish has been used for preclinical analysis of cancer drugs, [81][82][83][84] toxicological analysis of medicinal plant extracts, [85][86][87] and mainly in studies on several antipsychotic drugs. [88][89][90] A number of studies in this area focus on the toxicological effects of natural toxins, such as cyanotoxins 91,92 and cnidarian toxins 93,94 ; the latter and snake venom toxins may be useful for new drug development.…”