Purpose: Coordination compounds (compounds with metal-ligand chemical bond) have been widely used as a novel and interesting source for development of new drugs with several different activities. The dithiocarbamates are remarkable and well-known compounds with very high antifungal activity, but none dithiocarbamate, such as glycoluril- (L1) and uricdithiocarbamates (L2) have been used as ligands to generate copper complexes which could be used as possible new antifungal agents. The present work shows the results of the study of the antifungal activity of two copper dithiocarbamate complexes (C14H8N10O9S12Cu4 (1) and C18H4N12O18S16Cu6 (2)) against Aspergillus spp. Methods: Antifungal activities were evaluated against Aspergillus clavatus, A. fumigatus, A. niger, and A. tamarii, following the CLSI protocol with some modifications. Minimum Inhibitory Concentration (MIC) values were determined by microdilution of test-solution using commercial antifungal as positive control (amphotericin B and fluconazole). These promising antifungal agents are chemically prepared by an easy synthetic route. They were obtained in high yields and were completely characterized by the analytical and spectrometric techniques. Results: It is noteworthy that both complexes showed very quite high activity against A. clavatus, A. fumigates (ATCC and Clinic), A. niger and A. tamarii. The MIC values are 64 μg/mL against all Aspergillus species for equally complexes 1 and 2. As described before, we confirmed that the free ligand L2 showed not so high antifungal activity against Aspergillus: (A. fumigatus: 128 μg/mL). Through MIC comparison the results average proved the ligand L2 was 11-fold less active than complex 2, against A. fumigatus (ATCC and Clinic) and 6-fold less active against A. clavatus, A. niger and A. tamarii. The results above association with L1 and complex 1 no yet performed. Conclusions: These results show that the complexation of the dithiocarbamates L1 and L2 with copper(II) generates much more active complexes than the free dithiocarbamate. The copper complexes demonstrated promising antifungal activity against some important Aspergillus species.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)