Targeting the DNA-topoisomerase complex in a double-strike approach with a topoisomerase inhibiting moiety and covalent DNA binder

Abstract

Ru(II)(arene)-flavonoids with high in vitro antitumour activity were synthesised. These compounds are capable of inhibiting human topoisomerase IIα and binding covalently to DNA.

3-Hydroxyflavones vs. 3-hydroxyquinolinones: structure–activity relationships and stability studies on RuII(arene) anticancer complexes with biologically active ligands

“…Ruthenium complexes represent a promising class of metal-based 20 chemotherapeutics. The octahedral geometry of ruthenium, its binding ability to plasma proteins and the number of possible oxidation states in biological environments, makes it well suitable for drug design.…”

“…22 The Ru II (cym hydroxyflavones were found to exhibit not only anticancer activity in human cancer cell lines human topoisomerase IIα activity, which cytotoxic potency. 20 In order to study the impact of the nature of the halogenido ligands on the stability and cytotoxic activity, of Ru II (arene)X complexes with 3-hydroxyflavones has been synthesised. These properties are compared with those of structurally related 3-hydroxyquinolinone complexes featuring a 15 nitrogen atom in the heterocyclic ligand.…”

Synthesis and anticancer activity evaluation of η5-C5(CH3)4R ruthenium complexes bearing chelating diphosphine ligands

“…Complexes 4 and 5 were more active against A2780 cells, with IC 50 values close to cisplatin. The presence of the (CH 2 ) 5 OH chain in the Cp # compounds 2 and 5 produced no great effect on their anticancer activities, compared to those of the Cp* complexes 1 and 4. The best cytotoxicity was observed for the positively charged complex 3.…”

“…7,8 Samuelson and coworkers have published the use of η 6 -p-cymene ruthenium complexes with different diphosphines acting as either monodentate or chelating ligands, which showed good growth inhibitions against several cancer cell lines. 9 In contrast, fewer examples of η 5 -cyclopentadienyl (Cp) or pentamethylcyclopentadienyl (Cp*) compounds have been biologically evaluated. Sava reported the synthesis and activity against TS/A adenocarcinoma of the compounds [(η 5 -C 5 H 5 )Ru(pta) 2 Cl] and [(η 5 -C 5 Me 5 )Ru(pta) 2 Cl], as equivalents to the RAPTA complexes.…”

“…Sava reported the synthesis and activity against TS/A adenocarcinoma of the compounds [(η 5 -C 5 H 5 )Ru(pta) 2 Cl] and [(η 5 -C 5 Me 5 )Ru(pta) 2 Cl], as equivalents to the RAPTA complexes. 10 Compounds of the type [(η 5 (PP = 2 × PPh 3 or 1,2-bis(diphenylphosphino)ethane, L = planar nitrogen σ-bonded ligand and X = CF 3 SO 3 or PF 6 ) have been synthesised by Moreno et al and some of them show better cytotoxicities than cisplatin. [11][12][13] However, none of these Cp/Cp* ruthenium complexes has been tested under hypoxic conditions.…”