title: New chiral 4-substituted 2-cyanoethyl-oxazolines: synthesis and assessment of some biological activities.
abstract: This paper describes the synthesis of new enantiomerically pure 2-cyanoethyl-oxazolines in one step starting from a wide range of amino alcohols and 4-ethoxy-4-iminobutanenitrile with high to good yields (73-96%) via an appropriate procedure which can be used for a selective synthesis of mono-oxazolines. A simple operation as well as a practical separation is additional eco-friendly attributes of this method. All the synthesized compounds were identified and characterized with their physicochemical features and their spectral data ((1)H NMR, (13)C NMR and TOFMS ES(+)). Among the prepared mono-oxazolines, the mono-oxazoline (3a) [3-[(4S)-4-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile] was tested to detect some biological activities. This compound was studied in vitro given the various types of pharmacological properties characterizing these compounds such as antioxidant, antimicrobial and analgesic activities. The antioxidant activity and mechanism of (3a) were identified using various in vitro antioxidant assays including 1,1-diphenyl-2-picryl-hydrazyl (DPPH), and superoxide anion radicals (O2(-)) scavenging activity. In addition, compared to Quercetin, the tested synthetic product reveals a relatively-strong antiradical activity towards the DPPH (activity percentage of 81.22%) free radicals and significantly decreased the reactive oxygen species such as (O2(-)) formation evaluated by the non-enzymatic (nitroblue tetrazolium/riboflavine) and the enzymatic (xanthine/xanthine oxidase) systems. Related activity values were, respectively, 66% and 60.30%. The oxazoline (3a) showed a high ability to reduce the O2(-) generation and proved to be a very potent radical scavenger. On the other hand, the analgesic property of the 3[(4S)-benzyl-4,5-dihydro-1,3-oxazol-2-yl] propanenitrile (3a) was demonstrated. The subcutaneous administration of (3a) produced a significant reduction in the number of abdominal constrictions amounting to 73.81% in the acetic acid writhing test in mice. In addition to these advances, the oxazoline (3a) has been investigated as an antimicrobial agent. Our results showed that this molecule exhibited various levels of antibacterial effect against all the tested bacterial strains.
authors.affiliation: Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (UR11ES56), Faculté des Sciences, Avenue de l'environnement, 5019 Monastir, Tunisia.
authors.forename: Rym
authors.initials: R
authors.lastname: Hassani
authors.affiliation: Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (UR11ES56), Faculté des Sciences, Avenue de l'environnement, 5019 Monastir, Tunisia.
authors.forename: Yakdhane
authors.initials: Y
authors.lastname: Kacem
authors.affiliation: Laboratoire de biotechnologie et Valorisation de Bio Géo Ressources (LBVBGR), Institut Supérieur de Biotechnologie, ISBST BioTechPole Sidi Thabet Université Manouba, Ariana 2020, Tunisia.
authors.forename: Hedi
authors.initials: H
authors.lastname: Ben Mansour
authors.affiliation: Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (UR11ES56), Faculté des Sciences, Avenue de l'environnement, 5019 Monastir, Tunisia.
authors.forename: Hamed
authors.initials: H
authors.lastname: Ben Ammar
authors.affiliation: Laboratoire de Synthèse Organique Asymétrique et Catalyse Homogène (UR11ES56), Faculté des Sciences, Avenue de l'environnement, 5019 Monastir, Tunisia. Electronic address: bechirbenhassine@yahoo.fr.
authors.forename: Béchir
authors.initials: B
authors.lastname: Ben Hassine
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000378:metabolism; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D008826:Microbial Sensitivity Tests; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010147:Pain Measurement / Q000379:methods; D010851:Picrates / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D000700:Analgesics; D000900:Anti-Bacterial Agents; D001713:Biphenyl Compounds; D016166:Free Radical Scavengers; D010080:Oxazoles; D010851:Picrates; D013481:Superoxides; C004931:1,1-diphenyl-2-picrylhydrazyl
keywords: Amino alcohol; Biological activities; Iminoether; Monohydrochloride; Oxazoline