albicans and C. glabrata at a concentration of 0.49 μg ml−1; P3, the N,N′,N′′,N′′′-hexamethyl-derivative, also showed inhibitory activity PS-341 molecular weight against C. albicans and C. glabrata, but in higher concentrations (250 μg ml−1). The N,N′,N′′,N′′′-tetramethylated amine (P5) only inhibited the growth of C. glabrata, but its corresponding N,N′,N′′,N′′′-octamethyl derivative (P6) was also active against C. glabrata (125 μg ml−1) and it was the only compound active against C. parapsilosis. P2 and P4
showed no significant antifungal activity. The structure–activity relationship of the thioureido-substituted derivatives indicates that the molecular branching and the alkylation levels can influence the antifungal activity.
This study demonstrated that thioureido derivatives exhibited significant antifungal activity against Candida species and that they can be considered as a very promising bioactive lead compound to develop novel antifungal agents. “
“Pneumocystis spp. are peculiar fungi, because they lack ergosterol in their cytoplasmic membrane. Furthermore, they go through various sexual and non-sexual stages in a living host; the cysts, which are able to survive in the environment, are the infectious agents. The various species are more or less specific for a mammalian host. Pneumocystis jirovecii is pathogenic for humans. Transient colonisation of children and adults with this fungus occurs frequently. As a typical opportunist
it can induce an overt disease in immunocompromised patients only. In particular SCH772984 order those patients with an impaired cell-mediated immune system, namely AIDS patients or transplant recipients taking immunosuppressive agents, are affected. The leading clinical feature is a bilateral interstitial pneumonia characterised by progressive dyspnoea, tachypnoea and non-productive cough. Finally, the interstitial pneumonia will lead to hampered gas exchange resulting in a marked decrease in paO2 and consequently to a rather 3-oxoacyl-(acyl-carrier-protein) reductase low haemoglobin saturation. Pneumocystsis spp. do not grow on artificial media. Diagnosis is made by demonstration of fungal cells on microscopy preferentially by immunofluorescence staining or by the highly sensitive PCR method. A standardisation of the molecular methods is still lacking, since different DNA sequences are amplified in each case. Quantification by real-time PCR can help to differentiate between infection and mere colonisation. Among the common antifungals only the echinocandins are active at least against the cyst forms. The principal therapeutic agents remain, however, antibacterial and anti-parasitic agents, such as cotrimoxazole, clindamycin, primaquine, pentamidine and atovaquone. In addition, an improvement of the immunosuppression is warranted. Prophylaxis is indicated in those individuals with a prolonged cell-mediated immunodeficiency.