Unprecedented collateral sensitivity for cisplatin-resistant lung cancer cells presented by new ruthenium organometallic compounds

Abstract

Ru compounds exhibit collateral sensitivity in cisplatin-resistant NSCLC and increase cisplatin activity by inhibiting efflux pumps.

Ruthenium Complexes as Promising Candidates against Lung Cancer

“…Impressively, no damage was observed in major organs, including the kidney, in the mice treatment with Ru19 (6 mg/kg), while a mass of vacuolization in the cell cytoplasm of renal tubules were found in the cisplatin-treated mice, suggesting that the compound Ru19 exhibited lower systemic toxicity and was potentially more tolerated by animals than cisplatin [ 86 ]. Apart from targeting cisplatin-resistant cancer cells to address chemoresistance issue, Teixeira, R. G et al proposed a novel approach that organometallic Ru(II) compounds increased cisplatin cytotoxicity up to 1390-fold at nontoxic doses by inhibiting multidrug resistance-associated protein 1 (MRP1) and the P-glycoprotein 1 (Pgp) transporters [ 87 ]. It further promoted Ru(II) compounds as more valuable and prospective agents for lung cancer chemotherapy, in particular for those patients with cisplatin resistance.…”

Two out of Three Musketeers Fight against Cancer: Synthesis, Physicochemical, and Biological Properties of Phosphino CuI, RuII, IrIII Complexes

“…Thanks to the experience gained, alternative strategies have been developed that have led to the synthesis of numerous organometallic platinum-based compounds such as carboplatin and nedaplatin, with the aim of developing selectively toxic molecules towards cancer cells, hoping to generate an efficient bio-distribution and an inability to develop resistance conditions [6]. For this purpose, the correlation between the activity of the metal and its chemical environment is fundamental, in fact, the possibility of using a wide range of ligands paves the way for the study of new and different mechanisms of action, which is capable of limiting the general toxicity associated with these drugs while, in the meantime, maximizing the efficiency of cellular uptake [7][8][9][10][11]. In recent years, the research has underlined how a synthetic approach of this type allows great progress in the synthesis and optimization of competitive chemotherapy; however, the intrinsic reactivity and biological characteristics of platinum make it difficult to overcome many important therapeutic obstacles and the consequent achievement of an ideal pharmacology.…”

Metalloligand-based coordination polymer embedding the nitrosyl ruthenium complex for photoactive materials with bound nitric oxide

“…Functional materials based on ruthenium( ii ) complexes with a nitrosyl ligand have gained increasing attention for their numerous promising applications in data storage based on holography 1 and in photodynamic therapy (PDT) due to the generation of highly reactive ruthenium species and free nitric oxide (NO). 2–4 The light induced response of ruthenium nitrosyl complexes is based on the metal-to-ligand charge transfer (MLCT) which populates the antibonding π*(NO) orbital with significant ruthenium–NO antibonding character. 5,6 In the liquid phase, different dissociation mechanisms of the excited Ru–NO complexes are possible.…”