Synthesis, Hematological, Biochemical, and Neurotoxicity Screening of Some Mannich Base Hydrochlorides

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. Materials and 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). Conclusion: 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.