title: Synthesis, hematological, biochemical, and neurotoxicity screening of some mannich base hydrochlorides.
abstract: BACKGROUND
  Mannich bases are an important class of compounds in medicinal chemistry with a wide spectrum of biological activities, however, knowledge on their toxicity is limited.
  
  
  METHODS
  Two Mannich base hydrochlorides 1a (2-thienyl-β-dimethylaminoethyl ketone hydrochloride) and 1b (β-dimethylaminopropiophenone hydrochloride) were synthesized and characterized on the basis of their infrared and nuclear magnetic resonance spectral data. The potential effects of the synthesized compounds (5 mg/kg, i.p, during 30 days) on relative weight, hematological parameters, biochemical parameters, and neurotoxicity were tested using male Wistar rat.
  
  
  RESULTS
  The results showed that compound 1b alters body weight on the first 10 days (182%, P < 0.01) and on the last 10 days (107%, P < 0.01) of treatment. The same treatment decreases food intake (P < 0.01) and increases water intake (P < 0.05). Both compounds induced a deficit on rotarod test manifested by a decrease of grasping time (1a: 65.33%, P < 0.01; 1b: 60.55%, P < 0.01) and fall time (1a: 59.75%, P < 0.01; 1b: 56.81%, P < 0.01) only on the last day of training. Moreover, Mannich base 1b decreases the liver relative weight (22.24%, P < 0.01). It was also observed that both products decrease the total serum cholesterol (Ch) levels (1a: 52.87%, P < 0.01; 1b: 64.70%, P < 0.01). Interestingly, compounds 1a and 1b affect hematological parameters manifested by an increase of the number of white blood cells (1a: 32.29%, P < 0.05; 1b: 20.64%, P < 0.05) and red blood cells (RBCs) (1a: 12.57%, P < 0.05; 1b: 20.11%, P < 0.05), an increase of red cell hemoglobin concentration (1a: 10.48%, P < 0.05; 1b: 16.12%, P < 0.05) and of the volume occupied by RBCs or hematocrit (1a: 18.28%, P < 0.05; 1b: 15.56%, P < 0.05), and an increase of the number of platelets (1a: 16.80%, P < 0.05; 1b: 39.96%, P < 0.05) accompanied by a decrease in hemoglobin level only with the compound 1a (7.41%, P < 0.05).
  
  
  CONCLUSIONS
  These results show that both compounds 1a and 1b induced a hypoxia status associated to low level of Ch and liver toxicity. The deficit observed by rotarod could be explained by the myorelaxant effect of the used products.
authors.affiliation: Department of Biology, Laboratory of Integrative Physiology, Faculty of Sciences of Bizerta, University of Carthage, Tunisia ; Department of Chemistry, Laboratory of Heteroatom Organic Chemistry, Faculty of Sciences of Bizerta, University of Carthage, Tunisia.
authors.forename: Karima
authors.initials: K
authors.lastname: Lahbib
authors.affiliation: Department of Chemistry, Laboratory of Heteroatom Organic Chemistry, Faculty of Sciences of Bizerta, University of Carthage, Tunisia.
authors.forename: Iyadh
authors.initials: I
authors.lastname: Aouani
authors.affiliation: Department of Biology, Laboratory of Integrative Physiology, Faculty of Sciences of Bizerta, University of Carthage, Tunisia.
authors.forename: Hafedh
authors.initials: H
authors.lastname: Abdelmelek
authors.affiliation: Department of Chemistry, Laboratory of Heteroatom Organic Chemistry, Faculty of Sciences of Bizerta, University of Carthage, Tunisia.
authors.forename: Soufiane
authors.initials: S
authors.lastname: Touil
keywords: Biochemical; Mannich bases; hematological; hypoxia; myorelaxant; neurotoxicity