Résumé
Abouthiouline [1-Cyclohexyl-3[3-quinolyl]-2-thiourea] is a novel compound with antithyroid activity. Abouthiouline [ABL] was designed based on structure-activity relationships [E-state indexes] aimed at reducing the antioxidant properties of the compound by modification of acyclic thiourylene moiety. Antioxidant effects of currently available treatments such as propylthiouracil [PTU], methimazole [MTM] are associated with an incidence of agranulocytosis and aplastic anemia. In the present study, the preclinical toxicology of ABL was determined in mice and rats and compared with two reference compounds, namely, propylthiouracil, methimazole. Following short-term administration [7 days] to mice, ABL had minimal effects on biochemical parameters, although significant reductions in both total protein and albumin were noted. Long-term studies [30 days] in rats revealed significant effects of Abouthiouline, propylthiouracil and methimazole on serum electrolyte and glucose levels. Abouthiouline had no detrimental effects on hematologic parameters. However, total WBC count [propylthiouracil] and neutrophil levels [propylthiouracil and methimazole] were significantly decreased among other treatment groups. The results of this investigation suggest that Abouthiouline is a promising new antithyroid therapy with a reduced risk of hematologic toxicity that is associated with PTU and MTM. Further studies are warranted to assess the safety and efficacy of Abouthiouline