New Synthesis and Antiparasitic Activity of Model 5-Aryl-1-methyl-4-nitroimidazoles

Molecules

Haythem A. Saadeh¹  Ibrahim M. Mosleh¹ 

[1] ¹Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan ²Department of Biological Sciences, Faculty of Science, University of Jordan, Amman 11942, Jordan

关键词: 5-chloro-1-methyl-4-nitroimidazole;    arylboronic acids;    Suzuki coupling;    5-aryl-1-methyl-4-nitroimidazoles;    antiparasitic activity;   

DOI  :  10.3390/molecules14082758

来源: mdpi

【 摘 要 】

A number of 5-aryl-1-methyl-4-nitroimidazoles 5a-f have been synthesized in good yields by the Suzuki coupling reaction between 5-chloro-1-methyl-4-nitroimidazole (3) and arylboronic acids 4a-f, aided by dichlorobis-(triphenylphosphine)palladium(II), K₂CO_3, and tetrabutylammonium bromide in water at 70-80 °C. Compounds 5a-f were characterized by elemental analysis, NMR and MS spectral data. On the basis of in vitro screening data, 5-(3-chlorophenyl)-1-methyl-4-nitro-1H-imidazole (5f)exhibited potent lethal activity against Entamoeba histolytica and Giardia intestinalis with IC₅₀ = 1.47 µM/mL, a value lower by a factor of two than that of the standard drug, metronidazole. The boosted activity of 5f was not accompanied by any increased cytotoxicity.The rest of the series also exhibited potent antiparasitic activity with IC₅₀ valuesin the 1.72-4.43 µM/mL range. The cytotoxicity of the derivatives 5c and 5e was increased compared to the precursor compound, metronidazole, although they remain non-cytotoxic at concentrations much higher than the antiparasitic concentration of the two derivatives.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.