5-Nitro-2-furfuriliden derivatives as potential anti-Trypanosoma cruzi agents: Design, synthesis, bioactivity evaluation, cytotoxicity and exploratory data analysis
作者： Fanny Palace-Berl , Salomão Dória Jorge , Kerly Fernanda Mesquita Pasqualoto , Adilson Kleber Ferreira , Durvanei Augusto Maria
DOI: 10.1016/J.BMC.2013.06.017
关键词:
摘要: The anti-Trypanosoma cruzi activity of 5-nitro-2-furfuriliden derivatives as well the cytotoxicity these compounds on J774 macrophages cell line and FN1 human fibroblast cells were investigated in this study. most active series I II 4-butyl-[N'-(5-nitrofuran-2-yl) methylene] benzidrazide (3g; IC50=1.05μM±0.07) 3-acetyl-5-(4-butylphenyl)-2-(5-nitrofuran-2-yl)-2,3-dihydro,1,3,4-oxadiazole (4g; IC50=8.27μM±0.42), respectively. Also, compound 3g was more than standard drugs, benznidazole (IC50=22.69μM±1.96) nifurtimox (IC50=3.78μM±0.10). Regarding assay, presented IC50 value 28.05μM (SI=26.71) against cells. For showed 98μM (SI=93.33). On other hand, 4g a higher 400μM (SI >48), for its 186μM (SI=22.49). Moreover, an exploratory data analysis, which comprises hierarchical cluster (HCA) principal component analysis (PCA), carried out findings complementary. molecular properties that influenced compounds' grouping ClogP total dipole moment, pointing need lipophilic/hydrophilic balance designing novel potential anti-T. molecules.
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sci-hub.se 参考文章(40)
M. Januchowski, B. Pniewska, Structural Investigations of Nifuroxazide, p-Hydroxy-N'-(5-nitrofurfurylidene)benzhydrazide Polish Journal of Chemistry. ,vol. 72, pp. 2629- 2634 ,(1998)
François Denizot, Rita Lang, Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. Journal of Immunological Methods. ,vol. 89, pp. 271- 277 ,(1986) , 10.1016/0022-1759(86)90368-6
Gilbert Duclos, New York 1987 Liberte. ,vol. 42, pp. 25- 25 ,(2000)
Gilles Klopman, Ju-Yun Li, Shaomeng Wang, Mario Dimayuga, None, Computer Automated log P Calculations Based on an Extended Group Contribution Approach Journal of Chemical Information and Computer Sciences. ,vol. 34, pp. 752- 781 ,(1994) , 10.1021/CI00020A009
Hugo Cerecetto, Mercedes González, Synthetic Medicinal Chemistry in Chagas’ Disease: Compounds at The Final Stage of “Hit-To-Lead” Phase Pharmaceuticals. ,vol. 3, pp. 810- 838 ,(2010) , 10.3390/PH3040810
Salomão Dória Jorge, Marina Ishii, Fanny Palace-Berl, Adilson Kleber Ferreira, Paulo Luiz de Sá Júnior, Alex Alfredo de Oliveira, Ieda Yuriko Sonehara, Kerly Fernanda Mesquita Pasqualoto, Leoberto Costa Tavares, Preliminary in vitro evaluation of N′-(benzofuroxan-5-yl)methylene benzohydrazide derivatives as potential anti-Trypanosoma cruzi agents MedChemComm. ,vol. 3, pp. 824- 828 ,(2012) , 10.1039/C2MD20019H
Fávero Reisdorfer Paulai, Silvia Helena Pires Serrano, Leoberto Costa Tavares, Aspectos mecanísticos da bioatividade e toxicidade de nitrocompostos Química Nova. ,vol. 32, pp. 1013- 1020 ,(2009) , 10.1590/S0100-40422009000400032
Randall D. Tobias, Chemometrics: A Practical Guide ,(1998)
Salomão Dória Jorge, Fanny Palace-Berl, Andrea Masunari, Cléber André Cechinel, Marina Ishii, Kerly Fernanda Mesquita Pasqualoto, Leoberto Costa Tavares, Novel benzofuroxan derivatives against multidrug-resistant Staphylococcus aureus strains: Design using Topliss’ decision tree, synthesis and biological assay Bioorganic & Medicinal Chemistry. ,vol. 19, pp. 5031- 5038 ,(2011) , 10.1016/J.BMC.2011.06.034
PETER RALPH, ILONA NAKOINZ, Phagocytosis and cytolysis by a macrophage tumour and its cloned cell line. Nature. ,vol. 257, pp. 393- 394 ,(1975) , 10.1038/257393A0