Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds

Abstract

a b s t r a c tThe rational development of multinuclear arene ruthenium complexes (arene = p-cymene, hexamethylbenzene) from generation 1 (G 1 ) and generation 2 (G 2 ) of 4-iminopyridyl based poly(propyleneimine) dendrimer scaffolds of the type, DAB-(NH 2 ) n (n = 4 or 8, DAB = diaminobutane) has been accomplished in order to exploit the 'enhanced permeability and retention' (EPR) effect that allows large molecules to selectively enter cancer cells. Four compounds were synthesised, i. (6) were obtained in a similar manner from N-(pyridin-4-ylmethylene)propan-1-amine (L). The molecular structure of 5 has been determined by X-ray diffraction analysis and the in vitro anticancer activities of the mono-, tetraand octanuclear complexes 1-6 studied on the A2780 human ovarian carcinoma cell line showing a close correlation between the size of the compound and cytotoxicity.

Organometallic ruthenium-based antitumor compounds with novel modes of action

“…Such a compound could be useful to treat tumors that respond poorly to chemotherapeutic agents. Binuclear ruthenium-arene complexes (connected via pyridonebased chelators) were found to be highly active in a colorectal carcinoma cell line in the absence of any activity for the mononuclear counterparts [90e92], and multiple ruthenium-arene units bound to a dendritic polypyridyl core also show promise [93]. Such strategies have important implications and open the way for potential for future development.…”

Synthesis, X-ray crystal structure and cytotoxicity of a new tetranuclear ruthenium arene complex

“…Equally high cytotoxicities are reached with hexanuclear ruthenium assemblies which can also function as hosts for smaller drug molecules [21]. Tetranuclear ruthenium compounds with dendritic structures that seem more similar to compound 3 show IC 50 values of 40 µM which can still be regarded as active [19,22]. With an overall charge of 2+ complex 3 ranges between the charge-neutral dendrimers and the 4+ rectangular systems but its activity might still be limited by the possibilities to pass the cell membrane.…”

Half-sandwich ruthenium(II) complexes with N- and N,(N,O)-donor ligands: molecular, electronic structures, and computational study

“…In addition, the arene ligands stabilize the ruthenium ?2 oxidation state, which makes the corresponding complexes kinetically more labile when compared to those of ruthenium(III). Furthermore, the hydrogen bonding and p-stacking are important in mechanisms of biological activity and the complexes are able to present these interactions [15][16][17]. The benzimidazole and benzoxazole ligands are interesting due to their biological activity and the derivatives used as ligands in this work are a good representative of these derivatives.…”