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Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study
Synthesis and investigation of antifungal, anticonvulsant and anti-
Toxoplasma gondii
activities of ten novel (2-(cyclopropylmethylidene)hydrazinyl)thiazole
3a
–
3j
are presented. Among the derivatives, compounds
3a
–
3d
and
3f
–
3j
possess very high activity against
Candida
spp. ATCC with MIC = 0.015–7.81 µg/ml. Compounds
3a
–
3d
and
3f
–
3j
possess also very high activity towards most of strains of
Candida
spp. isolated from clinical materials with MIC = 0.015–7.81 µg/ml. The activity of these compounds is similar and even higher than the activity of nystatin used as positive control. Additionally, compounds
3c
and
3e
showed interesting anticonvulsant activities in the MES test, whereas compounds
3f
and
3i
demonstrated the anticonvulsant activity in PTZ-induced seizures. Noteworthy, none of these compounds impaired animals’ motor skills in the rotarod test. Moreover, thiazoles
3a
,
3h
, and
3j
showed significant anti-
Toxoplasma gondii
activity, with IC
50
values 31–52 times lower than those observed for sulfadiazine. The results of the cytotoxicity evaluation,
anti-Candida
spp. and anti-
Toxoplasma gondii
activity studies showed that
Candida
spp. and
Toxoplasma gondii
growth was inhibited at non-cytotoxic concentrations for the mouse L929 fibroblast and the African green monkey kidney (VERO) cells. Molecular docking studies indicated secreted aspartic proteinase (SAP) as possible antifungal target.