Synthesis and <i>in vitro</i> antiprotozoal activity of some 2- amino-4-phenyloxazole derivatives

Abstract

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 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopy and lowand 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 µM, while compound 3e (2-amino-4-(p-bromophenyl)-oxazole) showed the highest anti-trichomonal activity (IC50, 1.89 µM). 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.

Synthesis, Molecular Docking Studies and Cytotoxic Screening of Novel 2-Substituted Benzimidazole Derivatives

“…Oxazole is the parent compound for a vast class of heterocyclic aromatic organic compounds. These are azoles with an oxygen and a nitrogen separated by one carbon [9]. Oxazoles are aromatic compounds but less so than the thiazoles.…”

Recent Development and Green Approaches for Synthesis of Oxazole Derivatives: A Review

“…Oxazole and its derivatives are used in treatment of various types of illness [8] . Oxazole shows numerous biological activities such as anti-bacterial [9,10] , antifungal [11,12] , agonist of free fatty acid receptor (GPR40) [13] , highly selective histone deacetylase 6 (HDAC6) [14] , anticancer [15,16] , vegetative growth factor [17] , anti-tubercular, anti-leishmanial [18] , antiprotozoal [19] and anti-inflammatory [20] . Apart from these pharmacological activities, oxazole derivatives can also be used as anti-corrosive agent for stainless steel, dyes [21] , anti-ageing [22] , antioxidant [23] , metabolism enhancing agent [24] , pesticides and herbicides [6] .…”

“…This gives a very good chance of making 4, 5-disusbtituted oxazolines and 5-substituted oxazoles. Carballo et al [19] synthesised and tested seven derivatives of 2-amino-4-(p-substituted phenyl)oxazole as an antiprotozoal agent in vitro against Giardia lamblia and Trichomonas vaginalis. These oxazole derivatives were synthesized under microwave irradiation of a mixture of p-substituted 2-bromoacetophenone and urea in the presence of DMF.…”

2-Aminooxazole as a Novel Privileged Scaffold in Antitubercular Medicinal Chemistry

“…In this initial phase, α-bromo-4′-methylacetophenone ( 5 ) was used as the starting building block to react with urea ( 6 ) (Table ). This reaction has been reported in six studies, ,− and the yield for the formation of 7 was reported in only one case (21%) . For the first step, we focused our interest on optimizing parameters such as the solvent and the stoichiometric ratio and determining whether microwave (MW) irradiation is more efficient than conventional heating.…”

“…This reaction has been reported in six studies, 21,25−29 and the yield for the formation of 7 was reported in only one case (21%). 25 For the first step, we focused our interest on optimizing parameters such as the solvent and the stoichiometric ratio and determining whether microwave (MW) irradiation is more efficient than conventional heating. With regard to the solvent, first attempts were made using acetonitrile, ethanol, dimethoxyethane (DME), and PEG-400, as already reported in the literature for this kind of reaction.…”