Anticoagulant, antioxidant and cytotoxic potential of cinnamic acid and derivatives

INTRODUCTION: Since antiquity, natural products have been widely used to relieve symptoms and prevent numerous diseases. Early treatments for vascular disorders, including thrombosis, relied heavily on plant-derived substances, which later served as prototypes for the development of platelet aggregation inhibitors and coagulation-modulating agents. Among these bioactive constituents, phenolic compounds-abundantly found in various botanical sources-have gained prominence due to their well-established antioxidant properties and reported anticoagulant effects. Recent studies highlight that the structural diversity of phenolic acids, particularly cinnamic acid (CA) and its derivatives, offers a valuable chemical scaffold for developing new therapeutic agents targeting thrombogenesis and oxidative imbalance. OBJECTIVE: This study aimed to evaluate, in vitro, the pharmacological (anticoagulant and antioxidant) and toxicological (oxidant and cytotoxic) activities of cinnamic acid (CA) and five synthetic derivatives-4HDCN, 4MTCN, 3,4DHCN, 3,4DMCN, and 3H4MCN. METHODS: Anticoagulant activity was assessed using a semi-automated coagulometer by measuring clotting time after exposure of human plasma to each molecule. Antioxidant, oxidant, and cytotoxic (hemolytic) activities were determined using human erythrocytes from blood groups A, B, and O. Oxidative and antioxidant responses were quantified by spectrophotometry following exposure to phenylhydrazine as a pro-oxidant inducer. Hemolysis was evaluated at concentrations ranging from 0 to 400 mg/dL. RESULTS: In the anticoagulant assays, the derivative 3,4DHCN exhibited the strongest activity, prolonging clotting time to 176.6 s, slightly surpassing 3,4MTCN (165.6 s). All molecules demonstrated low or negligible oxidizing activity (