Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures
In this study,we designed and synthesized 12 novel aloperine derivatives with different core struc-tures.Among them,compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after y-H Huffman elimination of quaternary ammonium salt,and the structure was verified by X-single crystal diffraction.Furthermore,their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay.Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43,and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1.Schrödinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1.The results expanded the structural types of endocyclic aloperine and the function against coronavirus,and provided useful scientific data for the development of pharmaceutical applica-tions of these compounds.
quaternary ammonium salt aloperineSARS-CoV-2ten-membered ring aloperineTMPRSS2SR-B1
万方数据
维普
