Organometallic compounds in drug discovery: Past, present and future

International audienceIn this review, we present an overview of some of the medicinally-relevant organometallic drugs that have been used in the past or that are currently in clinical trials as well as an example of compounds that are currently in the initial stage of drug development. Three main classes of organometallic complexes have been chosen for discussion: antimicrobial organoarsenicals, antimalarial and anticancer ferrocene-containing compounds and anticancer catalytic organometallic complexes. The purpose of this review is to provide readers with a focus on the significant progress that has been made for each of these respective fields of medicine

Metal Dipyrrin Complexes as Potential Photosensitizers for Photodynamic Therapy

International audienceOver the last decades, the use of photodynamic therapy (PDT) for the treatment of various types of cancer as well fungal, viral and bacterial infections has received increasing attention. Despite its clinical success, the currently approved photosensitizers (PSs) are associated with poor water solubility, aggregation, low photostability and a long excretion time. To overcome these limitations, much research is devoted towards the development of PSs based on transition metal complexes. However, the majority of metals used for this purpose are rare and expensive. Therefore, it would be of high interest to develop effective PDT PSs based on cheap and abundant metals. In this article, the use of Cu(II) and Ni(II) dipyrrin complexes as potential PDT PSs against cancer is presented. As required for PDT applications, these complexes were found to have a strong absorption in the green spectrum and to be stable in an aqueous solution in the dark as well as upon light irradiation. Biological studies revealed that the complexes have a very low cytotoxic effect in the dark with a slight effect upon irradiation at 510 nm in human cervical carcinoma (HeLa) cells

Metal Complexes and Medicine: A Successful Combination

Since the start of our independent research at the Department of Chemistry of the University of Zurich in 2009, our group has been, among other topics, working on the use of metal complexes in medicinal chemistry. In this short review article, we highlight our recent achievements in the use of such compounds to fight the parasitic disease schistosomiasis

A solid phase-assisted approach for the facile synthesis of a highly water-soluble zirconium-89 chelator for radiopharmaceutical development

International audienceNuclear medicine has seen impressive growth in recent years. An important development in this field occurred through the application of new radionuclides, e.g., 89Zr (t1/2 = 78.4 h, β+ 0.396 MeV), the physical properties of which allow the use of antibodies as biological vectors for specific cancer targeting in combination with high resolution imaging by positron emission tomography (PET). The most commonly used chelator for 89Zr-based PET imaging is the hexadentate desferrioxamine (DFO) chelator. However, due to the instability of this complex, there has been a strong push towards the development of octadentate chelators. We report an ether derivative, oxoDFO*, resembling the motif of DFO with four hydroxamic acid groups for the binding of the radiometal and four ether linkages to increase the water solubility. Very importantly, the synthesis of this chelator follows a solid phase-assisted approach allowing for the development of an attractive synthetic methodology and widening the scope for the access to DFO-like chelators in highly efficient synthetic sequences

Biological Evaluation of the NIR‐Emissive Ruby Analogue [Cr(ddpd)2][BF4]3 as a Photodynamic Therapy Photosensitizer

International audiencePhotodynamic therapy relies on the bioavailability of photosensitizers with suitable photophysical, chemical and biochemical properties. Although the photophysical properties, stability and high water solubility of the chromium(III) complex [Cr(ddpd)2][BF4]3 (ddpd = N,N'-dimethyl-N,N'-dipyridin-2-ylpyridine-2,6-diamine) are very favorable, its photocytotoxicity against cancerous and non-cancerous cell lines has not yet been elucidated. We now report the cytotoxicity and photocytotoxicity of the complex [Cr(ddpd)2][BF4]3 against human cervical cancer cells, human primary glioblastoma cells, human glioblastoma astrocytoma cells and non-cancerous retinal pigment epithelium cells

Crystal structure of tris­(4,7-diphenyl-1,10-phenanthroline-κ2N,N′)cobalt(III) tris­(hexa­fluoro­phosphate) monohydrate

The title compound, [Co(C72H48N6)](PF6)3·H2O, crystallizes with one tripositive complex mol­ecule, three hexa­fluoro­phosphate anions and one solvent mol­ecule of water in the asymmetric unit. The N6 coordination set around the central CoIII atom defines a distorted octa­hedral environment. Four fluorine atoms of one hexa­fluoro­phosphate anion are disordered over two sets of positions with site-occupancy factors of 0.697 (5) and 0.303 (5). In the crystal, inter­molecular π–π stacking inter­actions, C—H...π, C—H...F and O—H...F and inter­actions are present

Lightening up Ruthenium Complexes to Fight Cancer?

In medicine, light is used in a medical treatment called photodynamic therapy (PDT) to treat some types of cancer and skin diseases. This technique generally allows for reduced side effects compared to traditional chemotherapy. However, PDT is not fully effective on hypoxic tumors (i.e. lacking oxygen). To overcome this important drawback, photoactivated chemotherapy (PACT) agents have been designed to obtain light-mediated cancer cell death via an oxygen-independent mechanism. Ruthenium complexes have already been and are currently deeply explored as traditional anticancer agents. However, as reported in this short review article, such compounds can also bring novel opportunities in the field of light-mediated cancer treatment. Herein, we report on our findings in the optimization of Ru(II) polypyridyl complexes as PDT and PACT agents for the potential treatment of cancer and, interestingly, also of bacterial infections

Towards Long Wavelength Absorbing Photodynamic Therapy Photosensitizers via the Extension of a [Ru(bipy) 3 ] 2+ Core

International audienceComplementary to classical treatment methods used against cancer, photodynamic therapy (PDT) has received increased attention over the last years. PDT relies on the generation of reactive oxygen species (ROS) upon light irradiation to trigger cell death. As the wavelength employed during such treatments directly influences the light penetration depth and therefore the possibility to treat deep seated tumours or large tumours, research efforts have been made towards the development of photosensitizers (PS) with an absorption in the phototherapeutic window (600-900 nm). To tackle this drawback, we report herein the preparation and characterisation of new Ru(II)-containing PDT PSs, that are based on a [Ru(bipy) 3 ] 2+ core (1; bipy: 2,2'-bipyridine) and that are extended with methyl groups (2) or vinyl dimethylamino groups (3). As anticipated with our design, we found a red-shift of 65 nm of the maximum absorption of complex 3 in comparison to complex 1. In addition, we report on the in-depth photophysical properties as well as (photo-)cytotoxicity against cervical cancerous HeLa cells of the investigated compounds