Biocompatible <i>de novo</i> indolylchalcones as platelet aggregation inhibition and diabetic wound healing agents

-acylated derivatives (20-27) are synthesised to explore their potential as multifunctional therapeutic agents. Compounds 24 and 25 demonstrate NOS activation (350-450% increase) and anti-platelet aggregation (40-45% inhibition), improving microvascular circulation and reducing thrombotic risk. They exhibited minimal cytotoxicity in NIH3T3 cells and negligible hemolytic activity. Notably, in diabetic wound models, compounds 24 and 25 accelerated wound healing by improving eNOS/NO levels, promoting angiogenesis, enhancing tissue regeneration, and modulating inflammatory cytokines, including marked reduction in IL-1β and TNF-α levels. Their dual functionality, vascular protection and regenerative potential positions indolylchalcones as promising candidates for future development in cardiovascular and wound-healing therapies.