Ruthenium-based nitric oxide-donating and carbon monoxide-donating molecules

Abstract

Objectives Over the past few years, the use of metallocomplexes for medical purposes has considerably grown. Because of its favourable characteristics, ruthenium has taken a significant place in this expanding field of research. Several ruthenium-containing metal compounds have been developed as delivery agents of physiological important molecules such as nitric oxide (NO) and carbon monoxide (CO). Key findings This review focuses on the (vaso)relaxant capacity of rutheniumbased NO-donating and CO-donating molecules in view of their potential usefulness in the treatment of cardiovascular diseases and erectile dysfunction. Summary Ruthenium seems to be a valuable candidate for the design of NOdonating and CO-donating molecules. To date, ruthenium remains of interest in drug research as the search for new alternatives is still necessary.

Nitric Oxide Donor-Based Cancer Therapy: Advances and Prospects

“…44 More details are described in the recent reviews by Franco 45 and Van de Voorde. 46 1,2,5-Oxadiazole N-oxides (furoxans) (Figure 2) are a class of NO donors that release NO in response to thiol-containing molecules, thus generating potent anticancer activity. Furoxans or benzofuroxans are used as synthetic precursors in the preparation of new NO donor hybrids, which have been reviewed elsewhere.…”

“…For example, trans -[Ru II (NO + )­(NH 3 ) 4 (Py)] 3+ induced apoptosis in HepG2 cells by decreasing membrane potential and ATP levels, generating ROS, and lowering mitochondrial permeability transition . More details are described in the recent reviews by Franco and Van de Voorde …”

Recent advances in photorelease complexes for therapeutic applications

“…In the past decades, photoactive CO-releasing molecules (PhotoCORMs) have aroused scientists’ interests because the CO molecule could be involved in immune and anti-inflammatory responses, as well as in vaso-relaxation. 60…”

Phenotypic switching prevention and proliferation/migration inhibition of vascular smooth muscle cells by the ruthenium nitrosyl complextrans-[Ru(NO)Cl(cyclam](PF6)2

“…The biological importance of NO had launched searches for NO carriers capable to deliver NO efficiently and in a controlled manner in physiological medium and aiming biological applications . NO donors are pharmacologically active substances that release NO, spontaneously or induced by chemical or photochemical reactions, differing by varied chemical and photochemical reactivities in physiological milieu and NO‐release kinetics . Among these NO donors, ruthenium tetraammine and tetraazamacrocycle nitrosyl complexes have favourable features, such as water solubility, stability even in aqueous solutions, low toxicity and for the possibility to control the reactivity of the coordinated NO by the careful choice of ligands around the RuNO moiety .…”

“…[19][20][21][22][23][24][25][26][27][28][29] NO donors are pharmacologically active substances that release NO, spontaneously or induced by chemical or photochemical reactions, differing by varied chemical and photochemical reactivities in physiological milieu and NO-release kinetics. [19][20][21][22][23][24][25][26][27][28][29][30][31] Among these NO donors, ruthenium tetraammine and tetraazamacrocycle nitrosyl complexes have favourable features, such as water solubility, stability even in aqueous solutions, low toxicity and for the possibility to control the reactivity of the coordinated NO by the careful choice of ligands around the RuNO moiety. [22,24,29,32] Such features make them attractive candidates as NO delivery agents, not only for therapeutic applications, as in cardiovascular devices, but also as pharmacological tools to investigate the role of NO in physiology and pathophysiology.…”