Systematic investigation of the antiproliferative activity of a series of ruthenium terpyridine complexes

Abstract

Due to acquired resistance or limitations of the currently approved drugs against cancer, there is an urgent need for the development of new classes of compounds. Among others, there is an increasing attention towards the use of Ru(II) polypyridyl complexes. Most studies in the literature were made on complexes based on the coordination of N-donating bidentate ligands to the ruthenium core whereas studies on 2,2´:6´, 2´´-terpyridine (terpy) coordinating ligands are relatively scare. However, several studies have shown that [Ru(terpy)2] 2+ derivatives are able bind to DNA through various binding modes making these compounds potentially suitable as chemotherapeutic agents. Additionally, light irradiation of these compounds was shown to enable DNA cleavage, highlighting their potential use as photosensitizers (PSs) for photodynamic therapy (PDT). In this work, we present the systematic investigation of the potential of 7 complexes of the type [Ru(terpy)(terpy-X)]2+ (X = H (1), Cl (2), Br (3), OMe (4), COOH (5), COOMe (6), NMe2 (7)) as potential chemotherapeutic agents and PDT PSs. Importantly, six of the seven complexes were found to be stable in human plasma as well as photostable in acetonitrile upon continuous light irradiation (480 nm). The determination of the distribution coefficient logP values for the 7 complexes revealed their good water solubility. Complex 7 was found to be cytotoxic in the micromolar range in the dark as well as to have some phototoxicity upon light exposure at 480 nm in non-cancerous retinal pigment epithelium (RPE-1) and cancerous human cervical carcinoma (HeLa) cells.

Metal dipyrrin complexes as potential photosensitizers for photodynamic therapy

“…Therefore, much efforts are devoted towards the development of transition metal complexes as PDT PSs. 40 The majority of complexes studied are based on Ru(II), [41][42][43][44][45][46][47][48][49][50][51] Os(II), [52][53][54] Ir(III), [55][56][57][58][59][60][61] Rh(III) [62][63][64] and Re(I). [65][66][67][68][69] As these metals are expensive, it would be of high interest to develop PSs based on cheap, abundant metals.…”

Synthesis, Characterization, Photoluminescence, Molecular Docking and Bioactivity of Zinc (II) Compounds Based on Different Substituents

“…Cancer is one of the leading causes of death worldwide, with more than 10 million people suffering from the disease yearly [ 1 , 2 , 3 ]. Since its introduction in medical practice, cisplatin has been one of the most effective drugs for the treatment of cancers [ 4 , 5 , 6 , 7 ]. The biological activity of cisplatin comes from the fact that its covalent binding with DNA leads to cell death or apoptosis.…”

Polymeric Bis(dipyrrinato) Zinc(II) Nanoparticles as Selective Imaging Probes for Lysosomes of Cancer Cells

“…The lipophilicity/hydrophilicity of the compounds was assessed by determination of the logP values between an aqueous phosphate buffer saline (PBS) phase and an octanol phase using the "shake-flask" method. [37][38] All compounds were majorly present in the organic phase with logP values between 0.4 -1.1 (Table S4), indicative of their lipophilicity. This result was expected as the complexes are uncharged and bear lipophilic aromatic systems.…”