Faculty of Medicine of Sfax

This work focuses on the synthesis and characterization of a new series of coumarin-hydrazone derivatives, as well as the evaluation of their inhibitory effects on platelet aggregation induced by adenosine diphosphate (ADP), arachidonic acid (AA), and collagen. Compounds 10 and 11 exhibit a significant inhibition of ADP-induced platelet aggregation. The AA-induced aggregation pathway was inhibited by compound 11 (45%), while none showed an inhibitory effect against collagen-induced aggregation. In addition, both compounds inhibited platelet binding to fibrinogen, CD62-P expression, and glycoprotein IIb/IIIa activation. The interaction of these compounds with their potential targets, P2Y12 and COX-1, was studied using a molecular docking approach. Furthermore, the ADMET properties of the compounds selected were evaluated in silico using Swiss ADME and ProTox-II tools. Selected active compounds demonstrated interesting pharmacokinetic and drug properties, indicating a favorable ADMET profile. In vitro and in silico results are in accordance. Toxicity on lymphocytes, erythrocytes, and platelets was evaluated for the two selected molecules and found to be safe. In summary, this study proposes two novel coumarin-hydrazone derivatives as new potential treatments to prevent cardiovascular events by acting on platelet adhesion, activation, and aggregation.

Adult onset Still disease (AOSD) is a rare systemic auto inflammatory disease of unknown origin. It is characterized by its clinical and biological polymorphism. Eliminating differential diagnoses is one of the most important steps when the diagnosis of adult Still’s disease is suggested, given the absence of clinical or laboratory signs to support the diagnosis; adult Still’s disease is a so-called “diagnosis of exclusion”. We conducted a retrospective study to describe clinical and laboratory features, treatment, course, and complications of AOSD in 65 Tunisian patients and to compare them to the literature. All patients responded to Yamaguchi criteria. There were 52% women (80%) and 13 men (20%). The mean age at diagnosis were 36.5 years old (range: 16-70 years). Fever was constant, associated with an altered general condition in 27 patients (41.5%). The other signs were polyarthritis (63.8%), skin involvement (83.1%) with a typic rash in 66.3%, throat sore (33.8%), lymphadenopathy (31.3%), splenomegaly (25%), hepatic involvement (50%) and pericarditis (18.5%). The inflammatory biological syndrome was constant. Leukocytosis greater than 10,000 Elt/mm³ was described in 87.3% of cases with polynuclear neutrophil > 80% in 63.6%. Hyperserotonemia was observed in 56 patients (96.5%). Treatment was based on corticosteroids, as a first line treatment, and methotrexate as a second line treatment. In terms of disease course, 68.3% of cases evolved to the systemic form and 31.7% of them to the chronic articular form. AOSD is a relatively benign disease. It can be life-threatening due to its severe systemic damage and functionally damaging due to its destructive joint damage.