Synthesis and in vitro antiprotozoal activity of some 2-amino-4-phenyloxazole derivatives

Purpose: To prepare some 2-amino-4-(p-substituted phenyl)-oxazole derivatives and to evaluate their in vitro antiprotozoal activity against Giardia lamblia and Trichomonas vaginalis. Methods: The 2-amino-4-(p-substituted phenyl)-oxazoles (a-g) were synthesized by microwave (MW) irradiation of mixtures of p-substituted 2-bromoacetophenones and urea in dimethylformamide (DMF). All compounds were identified by H-1 and C-13 nuclear magnetic resonance (NMR) spectroscopy and low-and high-resolution mass spectrometry (HRMS). NMR assignments were made based on heteronuclear single quantum coherence (HSQC) and heteronuclear multiple bond correlation (HMBC) experiments. Each synthesized compound's melting point was determined. Antiprotozoal activity against Giardia intestinalis and Trichomonas vaginalis was quantified using a rigorous and sensitive subculture method. The commercial drug, metronidazole, was used as positive control. The 50 % inhibitory concentration (IC50) of the antiprotozoal agents for each protozoa was determined. Results: Seven 2-amino-4-(p-substituted phenyl)-oxazoles (a-g) were synthesized. The most active compounds against G. lamblia was 2-amino-4-(p-benzoyloxyphenyl)-oxazole (3d) with an IC50 of 1.17 mu M, while compound 3e (2-amino-4-(p-bromophenyl)-oxazole) showed the highest anti-trichomonal activity (IC50, 1.89 mu M). Conclusion: The in vitro antigiardial activity of 2-amino-4-(p-benzoyloxyphenyl) oxazole was higher than that exhibited by metronidazole; however, it is necessary increase the number of synthetic derivatives in order to be able to determine their structure-activity relationship.