New synthesis and antiparasitic activity of model 5-aryl-1-methyl-4-nitroimidazoles.
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), K(2)CO(3, )and tetrabutylammonium bromide in water at 70-80 degrees 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 IC(50) = 1.47 microM/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 IC(50 ) values in the 1.72-4.43 microM/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.
Saadeh
Haythem A
HA
Chemistry Department, Faculty of Science, University of Jordan, Amman 11942, Jordan. h.saadeh@ju.edu.jo
Mosleh
Ibrahim M
IM
El-Abadelah
Mustafa M
MM
D000818:Animals; D000977:Antiparasitic Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*; D004748:Entamoeba histolytica / Q000187:drug effects; D016829:Giardia lamblia / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology*
D000977:Antiparasitic Agents; D009593:Nitroimidazoles; C052587:4-nitroimidazole
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