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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.

medicinal chemistry research

Thiazoles with cyclopropyl fragment as antifungal, anticonvulsant, and anti-Toxoplasma gondii agents: synthesis, toxicity evaluation, and molecular docking study