title: In vitro studies of the activity of dithiocarbamate organoruthenium complexes against clinically relevant fungal pathogens.
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. [C. albicans (two clinical isolates), C. glabrata, C. krusei, C. parapsolisis, C. tropicalis, C.dubliniensis (six clinical isolates)], Paracoccidioides brasiliensis (seven clinical isolates), Cryptococcus neoformans and Sporothrix schenckii. All synthesized complexes C1-C9 and also the free ligands L1-L9 were submitted to in vitro tests against those fungi and the results are very promising, since some of the obtained MIC (minimal inhibitory concentration) values were very low (from 10-6 mol mL-1 to 10-8 mol mL-1) against all investigated clinically relevant fungal pathogens, except for C. glabrata, that the MIC values are close to the ones obtained for fluconazole, the standard antifungal agent tested. Preliminary structure-activity relations (SAR) might be suggested and a strong influence from steric and lipophilic parameters in the antifungal activity can be noticed. Cytotoxicity assays (IC50) showed that the complexes are not as toxic (IC50 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).
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil. cdonnici@ufmg.br.
authors.forename: Claudio L
authors.initials: CL
authors.lastname: Donnici
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Luciano J
authors.initials: LJ
authors.lastname: Nogueira
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Araujo
authors.affiliation: Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Sheila Rodrigues
authors.initials: SR
authors.lastname: Oliveira
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Thais F F
authors.initials: TF
authors.lastname: Magalhães
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Miriam T P
authors.initials: MT
authors.lastname: Lopes
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Ana Cândida
authors.initials: AC
authors.lastname: Araújo e Silva
authors.affiliation: Instituto de Química da Universidade de São Paulo, Av. Lineu Prestes, 748, CEP 05508-900, São Paulo, SP, Brazil.
authors.forename: Ana Maria da Costa
authors.initials: AM
authors.lastname: Ferreira
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Cleide V B
authors.initials: CV
authors.lastname: Martins
authors.affiliation: Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil.
authors.forename: Maria A
authors.initials: MA
authors.lastname: de Resende Stoianoff
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000633:toxicity; D002175:Candida / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000494:pharmacology* / Q000633:toxicity; D006224:Cricetinae; D003455:Cryptococcus neoformans / Q000187:drug effects / Q000502:physiology; D006801:Humans; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D012428:Ruthenium / Q000737:chemistry; D013175:Sporothrix / Q000187:drug effects / Q000502:physiology; D013859:Thiocarbamates / Q000737:chemistry
chemical_list: D000935:Antifungal Agents; D056831:Coordination Complexes; D013859:Thiocarbamates; D012428:Ruthenium