Synthesis of 12-quinoline substituted andrographolide derivatives and their preliminary evaluation as anti-aggregation drugs

Based on the structure of the natural product andrographolide, a series of novel 12-quinoline substituted derivatives 9 were designed and synthesized. In preliminary biological evaluation, these synthesized compounds showed prominent anti-platelet aggregation activities in response to thrombin and adenosine diphosphate (ADP) agonists. Among them, compound 9o (inhibition rate 55.73%, IC50 0.36 µM/L) had the highest anti-platelet aggregation activity induced by ADP. Compound 9q (inhibition rate 54.31%, IC50 0.30 µM/L) showed the highest anti-platelet aggregation activity induced by thrombin. Most of the derivatives had no significant cytotoxicity. Our research results provide a novel candidate drug structure for anti-platelet aggregation and enrich the scope of application of andrographolide derivatives.