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Molecules 2014, 19(4), 5402-5420; doi:10.3390/molecules19045402
Article

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

1,* , 1, 1, 1, 2, 3, 3, 4, 2,5 and 2
Received: 26 February 2014; in revised form: 17 April 2014 / Accepted: 22 April 2014 / Published: 24 April 2014
(This article belongs to the Special Issue Ruthenium Complex)
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Abstract: The in vitro antifungal activity of nine dirutheniumpentadithiocarbamate complexes C1C9 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 C1C9 and also the free ligands L1L9 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).
Keywords: emerging infectious diseases; invasive fungal infections; dinuclear pentakis-dithiocarbamateruthenium complexes; antifungal susceptibility; cytotoxicity testing; Candida spp; Paracoccidioides brasiliensis; Cryptococcus neoformans; Sporothrix schenckii emerging infectious diseases; invasive fungal infections; dinuclear pentakis-dithiocarbamateruthenium complexes; antifungal susceptibility; cytotoxicity testing; Candida spp; Paracoccidioides brasiliensis; Cryptococcus neoformans; Sporothrix schenckii
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Donnici, C.L.; Nogueira, L.J.; Araujo, M.H.; Oliveira, S.R.; Magalhães, T.F.F.; Lopes, M.T.P.; Silva, A.C.A.; Ferreira, A.M.C.; Martins, C.V.B.; de Resende Stoianoff, M.A. In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens. Molecules 2014, 19, 5402-5420.

AMA Style

Donnici CL, Nogueira LJ, Araujo MH, Oliveira SR, Magalhães TFF, Lopes MTP, Silva ACA, Ferreira AMC, Martins CVB, de Resende Stoianoff MA. In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens. Molecules. 2014; 19(4):5402-5420.

Chicago/Turabian Style

Donnici, Claudio L.; Nogueira, Luciano J.; Araujo, Maria H.; Oliveira, Sheila R.; Magalhães, Thais F.F.; Lopes, Miriam T.P.; Silva, Ana C.A.; Ferreira, Ana M.C.; Martins, Cleide V.B.; de Resende Stoianoff, Maria A. 2014. "In Vitro Studies of the Activity of Dithiocarbamate Organoruthenium Complexes against Clinically Relevant Fungal Pathogens." Molecules 19, no. 4: 5402-5420.


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