5-Nitro-2-furfuriliden derivatives as potential anti-Trypanosoma cruzi agents: Design, synthesis, bioactivity evaluation, cytotoxicity and exploratory data analysis

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• 作者：Fanny Palace-Berl ; Salom?o D¨®ria Jorge ; Kerly Fern ; a Mesquita Pasqualoto ; Adilson Kleber Ferreira ; Durvanei Augusto Maria ; Rodrigo Rocha Zorzi ; Le ; ro de S¨¢ Bortolozzo ; Jos¨¦ ?ngelo Lauletta Lindoso ; Leoberto Costa Tavares
• 关键词：Trypanosoma cruzi ; 5-Nitro-2-furfuriliden ; Nifuroxazide ; Azomethine derivatives ; Oxadiazoline derivatives ; Molecular modeling
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2013
• 出版时间：1 September, 2013
• 年：2013
• 卷：21
• 期：17
• 页码：5395-5406
• 全文大小：1617 K

文摘

The anti-Trypanosoma cruzi activity of 5-nitro-2-furfuriliden derivatives as well as the cytotoxicity of these compounds on J774 macrophages cell line and FN1 human fibroblast cells were investigated in this study. The most active compounds of series I and II were 4-butyl-[N¡ä-(5-nitrofuran-2-yl) methylene] benzidrazide (3g; IC₅₀ = 1.05 ¦ÌM ¡À 0.07) and 3-acetyl-5-(4-butylphenyl)-2-(5-nitrofuran-2-yl)-2,3-dihydro,1,3,4-oxadiazole (4g; IC₅₀ = 8.27 ¦ÌM ¡À 0.42), respectively. Also, compound 3g was more active than the standard drugs, benznidazole (IC₅₀ = 22.69 ¦ÌM ¡À 1.96) and nifurtimox (IC₅₀ = 3.78 ¦ÌM ¡À 0.10). Regarding the cytotoxicity assay, the 3g compound presented IC₅₀ value of 28.05 ¦ÌM (SI = 26.71) against J774 cells. For the FN1 fibroblast assay, 3g showed IC₅₀ value of 98 ¦ÌM (SI = 93.33). On the other hand, compound 4g presented a cytotoxicity value on J774 cells higher than 400 ¦ÌM (SI >48), and for the FN1 cells its IC₅₀ value was 186 ¦ÌM (SI = 22.49). Moreover, an exploratory data analysis, which comprises hierarchical cluster (HCA) and principal component analysis (PCA), was carried out and the findings were complementary. The molecular properties that most influenced the compounds¡¯ grouping were C log P and total dipole moment, pointing out the need of a lipophilic/hydrophilic balance in the designing of novel potential anti-T. cruzi molecules.