Modulating the Anticancer Activity of Ruthenium(II)–Arene Complexes

Abstract

Following the identification of [Ru(η(6)-p-cymene)Cl2(1H,1H,2H,2H-perfluorodecyl-3-(pyridin-3-yl)propanoate)], a ruthenium(II)-arene complex with a perfluoroalkyl-modified ligand that displays remarkable in vitro cancer cell selectivity, a series of structurally related compounds were designed. In the new derivatives, the p-cymene ring and/or the chloride ligands are substituted by other ligands to modulate the steric bulk or aquation kinetics. The new compounds were evaluated in both in vitro (cytotoxicity and migration assays) and in vivo (chicken chorioallantoic membrane) models and were found to exhibit potent antivascular effects.

The development of anticancer ruthenium(ii) complexes: from single molecule compounds to nanomaterials

“…13). 160 7b was more cytotoxic than 7a in A2780 cells (IC 50 = 22.4 and 73 μM, respectively). These two complexes could selectively inhibit the migration of MDA-MB-231 tumor cells.…”

Anticancer Organometallic Osmium(II)‐p‐cymene Complexes

“…This was done by permeabilization of the cells and stainingw ith propidium iodide (PI-FACS). [36] l [a] Ru(h 6 -benzene)Cl 2 (1H,1H,2H,2H-perfluorodecyl-3-(pyridin-3-yl)propanoate) (shown), containingt wo independent moleculesi nt he asymmetric unit. Inductiono fa poptosis was most pronouncedf or 4 (58.3 %) and 7 (52.4 %), administrated at ad ose of 50 mm.T hese values are similart oa poptosis induction by sunitinib (at 10 mm), an anticancer and antiangiogenicc ompound in clinical use [45] which induced 62.6 %o fA 2780 cells to undergo apoptosis.…”

“…and orally against the murine colon carcinoma model CT-26, and the osmium(II)c omplex displayed significant growth-inhibitory activity in contrast to its ruthenium counterpart, which, at equimolar concentrations,w as inactive in this model.T he mitochondria-targeting organometallic trinuclear osmium cluster [Os 3 (CO) 10 (m-H)(m-S)C 9 H 6 N] (Figure 2), when administered by i.p. [35,36] Comparisons between the osmium and ruthenium complexes are made. [34] Herein we describe the synthesis, characterization, and in vitro and in vivo properties of as eries of osmium(II)-p-cymene complexes derivatized with lipophilic alkyl and perfluoroalkyl chains, which are structurally related to as eries of ruthenium(II) half-sandwich complexes.…”

Recent Considerations in the Application of RAPTA‐C for Cancer Treatment and Perspectives for Its Combination with Immunotherapies

“…[38,43,55] In 2011, a phase I dose escalation study for (N)KP1339 was initiated, including 16 patients with solid tumors that received one of six doses following a certain treatment schedule. [60,62,63] Although yet to enter clinical trials, a series of experimental drugs [66][67][68][69] that have been extensively evaluated in pre-clinical models are the so-called RAPTA compounds, with the general formula [Ru(arene)Cl 2 PTA] ( Figure 1). It should be noted that concentrations >400 mg induce a transient green discoloration of the patients' plasma.…”