Organometallic compounds in drug discovery: Past, present and future.

In 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.

Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis*.

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH -OXA), ruthenocene-containing (Rc-CH -OXA) and benzene-containing (Ph-CH -OXA) OXA derivatives.

One- and Two-Photon Phototherapeutic Effects of Ru Polypyridine Complexes in the Hypoxic Centre of Large Multicellular Tumor Spheroids and Tumor-Bearing Mice*.

During the last decades, photodynamic therapy (PDT), an approved medical technique, has received increasing attention to treat certain types of cancer. Despite recent improvements, the treatment of large tumors remains a major clinical challenge due to the low ability of the photosensitizer (PS) to penetrate a 3D cellular architecture and the low oxygen concentrations present in the tumor center. To mimic the conditions found in clinical tumors, exceptionally large 3D multicellular tumor spheroids (MCTSs) with a diameter of 800 μm were used in this work to test a series of new Ru polypyridine complexes as one-photon and two-photon PSs.

Synthesis, characterization and antiparasitic activity of organometallic derivatives of the anthelmintic drug albendazole.

Helminthiases, a group of neglected tropical diseases, affect more than one billion people mainly in tropical and subtropical regions. Moreover, major intestinal protozoa have a significant impact on global public health. Albendazole (ABZ) is a broad-spectrum anthelmintic recommended by the World Health Organisation (WHO).

Metal Compounds against Neglected Tropical Diseases.

Many first-line treatments for neglected tropical diseases identified by the World Health Organization (WHO) are limited by one or more of the following: the development of drug resistance, toxicity, and side effects, lack of selectivity, narrow therapeutic indices, route of administration, and bioavailability. As such, there is an urgent need to develop viable alternatives to overcome these limitations. The following review provides an overview of all existing metal complexes studied and evaluates the status of these complexes on the respective disease of choice.

Do bismuth complexes hold promise as antileishmanial drugs?

Even after 70 years, pentavalent antimonials sodium stibogluconate and meglumine antimoniate remain the most important and cost-effective antileishmanial drugs. However, the drugs cannot be delivered orally and treatment involves intravascular or intramuscular injections for 28 days under strict medical monitoring due to the toxicity of Sb(III). The main alternatives, amphotericin B, pentamidine and miltefosine, are expensive and not without their own problems.

Stability and toxicity of tris-tolyl bismuth(V) dicarboxylates and their biological activity towards Leishmania major.

A series of 29 tris-tolyl bismuth(v) di-carboxylato complexes of composition [Bi(Tol)3(O2CR)2] involving either ortho, meta or para substituted tolyl ligands have been synthesized and characterised. Of these 15 were assessed for their toxicity towards Leishmania promastigotes and human fibroblast cells, with ten then being subsequently assessed against parasite amastigotes. The carboxylate ligands are drawn from a series of substituted and biologically relevant benzoic acids which allow a comparison with earlier studies on [BiPh3(O2CR)2] and analogous Sb(v) [SbAr3(O2CR)2] (Ar = Ph and Tol) complexes.

Bismuth(III) α-hydroxy carboxylates: highly selective toxicity of glycolates towards Leishmania major.

Eight bismuth(III) complexes derived from the simple α-hydroxycarboxylic acids; gluconic (H₆-glu), tartaric (H₄-tar), mandelic (H₂-man), malic (H₃-mal) and glycolic (H₂-gly) have been synthesised and characterised. The complexes are formed through direct treatment of the organic acids with Bi(NO₃)3·5H₂O ([Bi(H₂-tar)(H₃- tar)] 2, [Bi(mal)(NO₃)(H₂O)₂] 6, [Bi(gly)(NO₃)(H₂O)] 8) or Bi(OtBu)₃ ([Bi(H-tar)(H₂O)₂] 1, [Bi(man)(H-man) (H₂O)] 4, [Bi2(H-mal)₃] 5, [Bi(gly)(H-gly)] 7), or through metathesis of the sodium salts with Bi(NO₃)3·5H₂O ([Bi(H3-glu)]₃). Reactions with both glucuronic and mucic acid proved to be unsuccessful.

Stability and toxicity of heteroleptic organometallic Bi(V) complexes towards Leishmania major.

Eleven heteroleptic Bi(V) complexes of the form [BiPh3(O2CR)2] have been synthesised and fully characterised. The carboxylate ligands are derived from a series of simple substituted benzoic acids, four of which are common non-steroidal anti-inflammatories (NSAIDs). The solid-state structures of eight of the complexes were determined by single crystal X-ray diffraction, and all were shown to adopt a typical trigonal bipyramidal geometry with chelating carboxylate ligands.