These findings are similar to those previously reported after

treatment of Candida spp. with different azoles [25–28]. Borges and co-workers [27] reported that exposure of Candida albicans to ITC leads to primary alterations Trichostatin A at the cell periphery and the appearance of vacuoles in the cytoplasm, which may be lipid inclusions. These changes were usually accompanied by an increase in the cell volume and impaired cell division. In addition, studies by Hazen and co-workers [28] revealed that Candida treated with FLC shows a distinct retraction of the membrane from the cell wall. On the other hand, C. albicans treated with low concentrations of AMB shows chromatin condensation and margination, separation of the nuclear envelope, and nuclear fragmentation [29]. High concentrations of AMB induce cellular changes PF 01367338 characteristic of necrosis, showing many large vacuoles [29]. Additionally, Bahmed and co-workers

[30] demonstrated an increase in cell wall thickness of Candida yeasts, which may be related to alterations in the cell wall composition induced by the treatment with AMB. In addition, similar to our findings, the appearance of multivesicular bodies and myelin-like structures were reported after treatment of Leishmania [11, 12] and T. cruzi [31] with AZA and EIL. Staining with Nile Red revealed the presence of lipid accumulation in the cytoplasm after treatment with 24-SMTI, confirming that these compounds induce a perturbation in lipid biosynthesis. Similar observations have recently been made as the result of treatment of Leishmania amazonensis with 24-SMTI, which induced several abnormalities in the lipid content, with the accumulation of steroid intermediate molecules [12]. In addition, staining of DNA with DAPI indicates a profound alteration in the cell cycle after treatment

aminophylline with AZA and EIL. Candida yeasts produced unfertile buds that remained closely associated with the mother cell, and appeared with or without various nuclei. The nucleus may also have an altered shape and/or with abnormal chromatin condensation that might be associated with apoptosis cell death, as previously described after treatment of C. albicans with AMB [29]; and also after treatment of Tritrichomonas foetus with hydrogen peroxide [32]. The presence of many cells with more than one nucleus may also indicate that ergosterol biosynthesis inhibitors are interfering with cytokinesis. In fact, it was previously found that ergosterol levels modulate the activity of protein kinases such as pp60v-src and also the levels of cAMP, both of which are directly related to the control of the cell cycle [33, 34]. In addition, some studies have shown that drugs such as griseofulvin and Screening Library nocodazole, which interfere with the assembly of cytoskeleton components, induce alterations in the cell cycle and apoptosis cell death [35–37].