Synthesis of Chromeno[2,3-d]pyrimidine-2,4(3H)-dion Derivatives Fused with Indole Moiety as Potent Biological Agents

Objective: In this paper we have reported the synthesis of novel chromeno[2,3-d]pyrimidine-2,4(3H)dione derivatives (IVa-IVh) by three component reaction between barbituric acid, indole and aromatic aldehydes useing L-Proline as a catalyst. Methods: The structures of synthesized compounds were confirmed by spectroscopic techniques. The synthesized compounds were examined for Acetyl CoA inhibitory activity. Results and Discussion: Compound (IVb) showed good activity as compared to other compounds. Also, the synthesized compounds were examined for Anti-inflammatory activity against MMP-2 and MMP-9 using gelatin zymography; in which compound (IVd) exhibited very good efficacy viz inhibited MMP-2 and MMP-9 to 80 and 50%, respectively. Furthermore, the molecular docking studies were carried out using a 1PG4 receptor. Conclusions: From the molecular docking study it was found that compound IVa exhibits a best dock confirmation with higher binding affinity (-11.0 kcal/mol) by establishing 3 hydrogen bonds.