Visible-Light-Driven Photocatalyst-Free Multicomponent Reactions: Green Synthesis of Tetraketones as Potent Antiviral Agents through Virtual Screening, Molecular Docking, and MD Simulations

Herein, we report a photocatalyst (PC)-free, visible-light (30 W LED)-driven green and sustainable synthesis of a series of functionalized tetraketones by a one-pot multicomponent reaction at room temperature. The ethanol-mediated reaction of variably substituted aromatic/heteroaromatic, aliphatic aldehydes, and dimedone furnished the biologically relevant tetraketones in very good yields (72–92%) in 10 min to 5 h. The key advantages of the current process include its environmentally benign aspect, operational simplicity, easy isolation of the products, high yields, PC- and metal-free aspects, employment of visible light as a green and sustainable energy source, and gram-scale synthesis. The synthesized tetraketones are further subjected to in silico studies which investigate the potential of synthesized tetraketones as inhibitors targeting CHIKV nsP2 and DENV NS2B-NS3 viral proteases through a combination of virtual screening, molecular docking, and MD simulation studies. We evaluated the binding affinity and inhibitory efficacy of the synthesized tetraketones against the viral proteases: CHIKV nsp2 and DENV NS2B-NS3. Pleasingly, our findings demonstrate that compound 3f exhibits promising inhibitory activity, with binding affinities of −24.22 and −29.39 kcal/mol for CHIKV nsp2 and DENV NS2B-NS3 protease, respectively. This result highlights the potential of tetraketones as novel antiviral agents against CHIKV and DENV.