In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens

Abstract

Abstract:The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1-C9 was investigated and assessed for its activity against four different fungal species with clinical interest and related to invasive fungal infections (IFIs), such as Candida spp. influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC 50 ) showed that the complexes are not as toxic (IC 50 values are much higher-30 to 200 fold-than MIC values). These ruthenium complexes are very promising lead compounds for novel antifungal drug development, especially in IFIs, one of most harmful emerging infection diseases (EIDs).

Cationic RuII Cyclopentadienyl Complexes with Antifungal Activity against Several Candida Species

“…[21] Although numerous compounds based on various other metals (Cu, Ni, Zn, Co, Ag, Pd, etc) were previously reported for their activity against a wide range of fungal species including Candida, [22][23][24][25][26][27][28][29][30] our long-standing interest in the biological activity of ruthenium complexes prompted us to investigate the promising antifungal potential of compounds based on this particular metal. [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] It is noteworthy that ruthenium complexes are currently extensively studied for their anticancer properties and are even now considered as potential alternatives to cisplatin, a chemotherapeutic agent currently widely used in clinical settings. [51][52][53][54][55] For instance, Turel et al reported Ru II complexes bearing antifungal azole-containing drugs clotrimazole, miconazole, and tioconazole that could inhibit the growth of Curvularia lunata.…”

“…[33] Notably, several ruthenium species were also previously studied for their potential anti-Candida properties ( Figure 1). [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50] Some of the first examples were reported by Günal et al (1999) and consisted of a series of Ru II -cymene complexes with promising activities against different fungal species including C. albicans and C. tropicalis. [44] Since then, most reports of ruthenium species with an anti-Candida activity ( Figure 1) showed a superior antifungal activity for the complexes compared to their corresponding ligands, suggesting an important role of the ruthenium moiety in the observed antifungal activity.…”

Targeting the Homoserine Dehydrogenase of Paracoccidioides Species for Treatment of Systemic Fungal Infections

“…The resistance of systemic fungi, especially P. brasiliensis, to the drugs currently used to treat paracoccidioidomycosis has become a public health problem, since there are already reports that P. brasiliensis strains are resistant to azoles (22)(23)(24). A fact that further aggravates this situation is that the drug arsenal currently available to combat the fungus is quite limited compared to the arsenal available for antibacterial chemotherapy.…”

“…These three molecules exhibited MIC values of 8 to Ͼ256 g · ml Ϫ1 and 16 to Ͼ256 g · ml Ϫ1 for strains of P. brasiliensis and P. lutzii, respectively. In another work with dirutheniumpentadithiocarbamate derivatives, Donnici et al (24) found that MIC values for Pb18 strains of P. brasiliensis varied from 16 to 128 g · ml Ϫ1 , a The results for residues with a higher frequency of contact are in bold.…”

Special Issue on Ruthenium Complexes

“…Fernando Rogério Pavan et al [ 12 ] reported on the in vitro anti-tuberculosis activity and cytotoxicity of ruthenium compounds encapsulated in nanostructured lipid systems composed of cholesterol, surfactant, and aqueous phase. Finally, Claudio L. Donnici [ 13 ] investigated the in vitro antifungal activity of a series of ruthenium dithiocarbamate complexes against different fungal species of clinical interest and related to invasive fungal infections. Very promising results were obtained and a preliminary structure–activity relationship was established.…”