Synthesis, in vitro inhibitory activity towards COX-2 and haemolytic activity of derivatives of Esculentoside A

Twenty-one derivatives of Esculentoside A were synthesized. The conversion of the carboxylic acid into amides can highly enhance their inhibitory activity towards COX-2, and also increased the haemolytic activity. Esculentoside A (EsA) has been reported to possess anti-inflammatory activity and selective inhibitory activity towards cyclooxygenase-2. A series of derivatives of EsA were synthesized by converting the C-28 carboxylic acid group into amides. The haemolytic activity and inhibitory activity towards cyclooxygenase-2 were evaluated in vitro. The SAR study of the derivatives was conducted and showed that introducing aromatic ring to EsA greatly enhanced its biological activity. Compound 23 showed higher inhibitory activity than Celecoxib and EsA, but lower haemolytic toxicity than EsA.