Table 1.
Effect of test compounds on planktonic growth of the clinical isolates belonging to the C. haemulonii complex.
| Compounds | Candida haemulonii | Candida haemulonii var. vulnera | Candida duobushaemulonii | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MIC (mg/L) | GM-MIC (mg/L) | MIC (mg/L) | GM-MIC (mg/L) | MIC (mg/L) | GM-MIC (mg/L) | Overall GM-MIC (mg/L) | |||||||
| LIP Ch4 | LIP Ch7 | LIP Ch12 | LIP Ch5 | LIP Ch9 | LIP Ch11 | LIP Ch1 | LIP Ch6 | LIP Ch8 | |||||
| Caspofungin | 0.5 | 0.25 | 0.125 | 0.25 | 0.25 | 0.25 | 0.5 | 0.315 | 0.125 | 0.25 | 0.125 | 0.157 | 0.23 (0.18 μM) |
| 1,10-phenanthroline (phen) | 1 | 1 | 1 | 1 | 1 | 1 | 0.5 | 0.79 | 1 | 1 | 1 | 1 | 0.93 (5.16 μM) |
| 1,10-phenanthroline-5,6-dione (phendione) | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 4 | 2 | 2.52 | 2.16 (10.27 μM) |
| CuCl2 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 (>23 μM) |
| MnCl2 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 (>28 μM) |
| AgNO3 | 1 | 0.5 | 1 | 0.79 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 0.5 | 1 | 0.63 | 0.63 (3.93 μM) |
| COPPER(ii) CHELATES | |||||||||||||
| [Cu(ph)(phen)(H2O)2] (1) | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 (>72 μM) |
| [Cu(ph)(phen)2].3H2O.2EtOH (2) | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 | >32 (>43.52 μM) |
| [Cu(isoph)(phen)2].6H2O.EtOH (3) | 8 | 8 | 16 | 10.08 | 4 | 8 | 8 | 6.35 | 4 | 8 | 4 | 5.04 | 6.86 (9.21 μM) |
| [{Cu(phen)2}2(terph)](terph).13.5H2O.2EtOH (4) | >32 | >32 | >32 | >32 | 32 | 32 | 32 | 32 | >32 | >32 | >32 | >32 | >32 (>21.92 μM) |
| [Cu2(oda)(phen)4](ClO4)2.2.76H2O.EtOH (5) | 8 | 8 | 16 | 10.08 | 8 | 16 | 8 | 10.08 | 8 | 8 | 8 | 8 | 9.33 (7.09 μM) |
| [Cu(phendione)3](ClO4)2.4H2O (6)* | 16 | 16 | 16 | 16 | 4 | 8 | 8 | 6.35 | 8 | 16 | 4 | 8 | 9.33 (9.65 μM) |
| {[Cu(3,6,9-tdda)(phen)2].3H2O.EtOH}n (7) | 4 | 4 | 2 | 3.17 | 2 | 2 | 4 | 2.52 | 2 | 2 | 2 | 2 | 2.52 (3.37 μM) |
| MANGANESE(ii) CHELATES | |||||||||||||
| [Mn(ph)(phen)(H2O)2] (8) | 8 | 4 | 4 | 5.04 | 4 | 4 | 4 | 4 | 8 | 4 | 4 | 5.04 | 4.67 (10.71 μM) |
| [Mn(ph)(phen)2(H2O)].4H2O (9) | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 (2.98 μM) |
| [Mn2(isoph)2(phen)3].4H2O (10) | 8 | 8 | 4 | 6.35 | 4 | 4 | 4 | 4 | 8 | 8 | 4 | 6.35 | 5.44 (5.15 μM) |
| {[Mn(phen)2(H2O)2]}2(isoph)2(phen).12H2O (11) | 4 | 2 | 2 | 2.52 | 4 | 2 | 2 | 2.52 | 2 | 4 | 2 | 2.52 | 2.52 (1.54 μM) |
| [Mn(tereph)(phen)2].5H2O (12) | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 | 4 (5.96 μM) |
| [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2]4H2O (13) | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 4 | 2 | 2.52 | 2.16 (0.87 μM) |
| {[Mn(3,6,9-tdda)(phen)2].3H2O.EtOH}n (14) | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 2 | 4 | 4 | 2 | 3.17 | 2.33 (3.15 μM) |
| SILVER(i) CHELATES | |||||||||||||
| [Ag(phendione)2]ClO4(15)* | 1 | 1 | 1 | 1 | 2 | 1 | 1 | 1.26 | 2 | 2 | 2 | 2 | 1.36 (2.16 μM) |
| [Ag2(3,6,9-tdda)(phen)4].EtOH (16) | 1 | 1 | 1 | 1 | 1 | 0.5 | 1 | 0.79 | 2 | 1 | 1 | 1.26 | 1 (0.83 μM) |
| [Ag(phen)2]ClO4 (17)* | 1 | 1 | 1 | 1 | 1 | 0.5 | 0.5 | 0.63 | 2 | 1 | 2 | 1.59 | 1 (1.76 μM) |
| [Ag2(phen)3(udda)].3H2O (18) | 0.125 | 0.25 | 0.125 | 0.16 | 0.5 | 0.125 | 0.25 | 0.25 | 0.5 | 0.25 | 1 | 0.5 | 0.27 (0.26 μM) |
All the MIC values are shown as mg/L. GM-MIC—Geometric mean of the compound MIC values (mg/L) for each species of Candida haemulonii complex. The last column presents the overall MIC geometric mean values for each of the test compounds across all nine strains of the C. haemulonii complex. The MIC values (μM) between copper(II), manganese(II) and silver(I) chelates were statistically significant (P = 0.038, one-way ANOVA).
Statistical analysis using one-way ANOVA evidenced that the MIC values of this compound among the three species were significant (compound 6—P = 0.05; compound 15—P = 0.02; compound 17—P = 0.04) the uncoordinated dicarboxylic acid ligands (ie phthalic, isothphalic, terethphalicoctanedioic and 3,6,9-trioxaundecanedioic acids) do not exhibit anti-Candida capability (Devereux et al., 2000). The effect of classical antifungal agents against all these clinical strains of C. haemulonii species complex used herein were previously published by our research group (Ramos et al., 2015). In a general way, all the fungal strains were resistant to azoles (fluconazole, itraconazole and voriconazole) and amphotericin B; on the other hand, caspofungin was active against them. So, caspofungin was used as a positive control of classical antifungal agent able to inhibit the growth of all the clinical isolates used herein.