Organometallic Compounds in Chemotherapy Against Leishmania

Abstract

Leishmaniasis today constitutes a major health problem and a mammoth task in the field of drug discovery. This is due to the limited arsenal of effective anti-leishmanial chemotherapeutics, painful parenteral administration, exorbitant price and numerous adverse side effects associated with current clinically established leishmanicidal drugs. These include meglumine antimoniate (Glucantime®), stibogluconate (Pentostam®), liposomal amphotericin B (AmBisome®) and miltefosine. Also, due to the frequent manifestation of chemo-resistance in some countries, an exigent and relentless requisite is to develop innovative, innocuous and valuable anti-leishmanials. Metal compounds still offer excellent prospects for finding new ‘leads’ against parasitic diseases, including leishmaniasis. A number of organometallic compounds have already been evaluated in the therapeutic area to treat and eradicate leishmaniasis. In the last two decades, several new antimony-, bismuth-, tin-, tellurium-, palladium-, rhodium-, iridium-, ruthenium- and iron-based organometallic compound have been evaluated for their anti-leishmanial activity, showing great promise for the discovery of new anti-leishmanial drugs. This chapter outlines the old and new trends, and future perspectives for this exciting research field.

Models of the putative antimony(v)–diolate motifs in antileishmanial pentavalent antimonial drugs

“…A similar upfield shift is observed for both of the Sb compounds derived from R,S diols (2 and 3). In contrast, the compounds derived from the R,R/S,S diols exhibited either a smaller upfield shift (4) or a marked downfield shift (5). We observed a similar distinction between 2/3 and 4/5 in the 1 H NMR resonances of the OCH nuclei of the diols and bound diolates (Fig.…”

“…Sb-containing therapeutics are still used, however, to treat the neglected tropical disease leishmaniasis. 5 Up to a million new cases of leishmaniasis are reported annually, mostly in low- and middle-income countries. 6 The Sb-containing antileishmanial drugs meglumine antimoniate (Glucantime) and sodium stibogluconate (Pentostam) are collectively known as the pentavalent antimonials.…”

Metal Compounds against Neglected Tropical Diseases

“…The first-line treatment for leishmaniasis consists of the pentavalent antimonial drugs sodium stibogluconate (Pentostam, GlaxoSmithKline) (Figure ) and meglumine antimonate (Glucantime, Sanofi-Aventis) (Figure ). These pentavalent antimonials are administered intravenously for 28 consecutive days (20 mg of Sb/kg/day) and are variable in their efficacy against both VL and CL . In 1981, Croft showed that, for sodium stibogluconate, the active compound comes from the trivalent form of the drug .…”

Polyfunctional Sterically Hindered Catechols with Additional Phenolic Group and Their Triphenylantimony(V) Catecholates: Synthesis, Structure, and Redox Properties

“…Thus, the synthesis and study of the properties of thiolated dioxiolene ligands and metal complexes based on them is relevant in view of the diversity of the properties manifested. Antimony(III/V) derivatives are used as antiparasitic agents in the treatment of leishmaniasis [53], and have potential as antitumor, cytotoxic, and antibacterial substances [54,55]. Along with biological activity, antimony complexes are promising compounds for the design of functional materials.…”