Abstract
Free radicals like reactive oxygen species (ROS) and reactive nitrogen species (RNS) cause cellular damage and contribute to thromboembolic diseases by promoting platelet activation and aggregation. Compounds that scavenge free radicals can reduce oxidative stress, decreasing platelet aggregation and thrombus formation. Despite their beneficial biological activities, indoles have clinical limitations due to poor bioavailability, solubility, rapid metabolism, and limited membrane permeability. We designed a new class of indole derivatives (10a-j) with a triazole linker and various amino acids to overcome these issues. These conjugates enhance solubility and bioavailability and possess antioxidant properties. Compounds 10f, 10g, and 10h showed improved permeability and significant anti-platelet aggregation effects, comparable to aspirin. These findings highlight the potential of these new indole derivatives as effective antithrombotic agents, warranting further exploration of their mechanisms and therapeutic applications.