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

Molecules

Claudio L. Donnici⁴  Luciano J. Nogueira⁴  Maria Helena Araujo⁴  Sheila Rodrigues Oliveira⁴  Thais F. F. Magalh฾s³  Miriam T. P. Lopes²  Ana Cândida Araújo e Silva²  Ana Maria da Costa Ferreira¹  Cleide V. B. Martins³ 

[1]Instituto de Química da Universidade de São Paulo, Av. Lineu Prestes, 748, CEP 05508-900, São Paulo, SP, Brazil

[2]Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil

[3]Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil

[4]Departamento de Química, Instituto de Ciências Exatas, Universidade Federal de Minas Gerais, Av. Antonio Carlos, 6627, CEP 31270-901, Belo Horizonte, MG, Brazil

关键词: emerging infectious diseases;    invasive fungal infections;    dinuclear pentakis-dithiocarbamateruthenium complexes;    antifungal susceptibility;    cytotoxicity testing;    Candida spp;    Paracoccidioides brasiliensis;    Cryptococcus neoformans;    Sporothrix schenckii;   

DOI  :  10.3390/molecules19045402

来源: mdpi

【 摘 要 】

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).

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.