Protocatechuic acid derivatives in wound healing: Seven protocatechuic acid derivatives are synthesized using click chemistry, amine coupling, and esterification reactions. All the synthesized compounds along with the starting compound are screened for their antioxidant properties in cell line. One of the compounds demonstrated high potential in wound healing application in rats.

Treatment of chronic wounds is a potential healthcare problem, affecting people globally. Traditional methods of wound healing are prone to several limitations, like infections, oxidative stress, and development of secondary wounds. Management of oxidative stress is an interesting platform to deal with chronic wounds. For this study, novel derivatives of protocatechuic acid, a naturally occurring phenolic acid, were designed by modifying the carboxylic acid moiety while preserving the hydroxyl groups for radical scavenging. So, a series of amide conjugates were synthesized by incorporating various amine moieties. Glucose conjugates were obtained through both click chemistry and direct coupling strategies and a chlorinated derivative was also prepared. The antioxidant potential of the compounds was screened using DPPH assay, followed by in vitro DCFDA assay on HEK-293T cell line. Top 5 lead molecules were checked for biocompatibility through MTT assay, which provided us with top 2 leads, Compounds 12 and 17 which were examined for a wound healing study on Wistar rats along with the starting compound 1. It was observed that Compound 17 demonstrated excellent wound tissue regeneration on day 12, as compared to the control group, suggesting the promising role of triazole and glucose moieties conjugation for relieving oxidative stress and wound management.