Study On Anti-HIV-1 Virus Activity Of Oxime Compounds Based On Multi-Target Docking

Objective:To develop alternative or pre-exposure drugs for HIV-infected patients with drug resistanc group or high-risk group.Methods:26 compounds with oxime,oxime ether and oxime ester structures were docked and scored on HIV-1 protein gp120,gp41 and spike to find HIV-1 entry inhibitor by MOE software.Toxicity of these compounds to TZM-bl cells was detected by Cell Counting Kit-8 kit on the bench.The inhibitory effect of these compounds to HIV-1 virus was established by TZM-bl/HIV-1_IIIBcell model in vitro.The structure-activity relationship was tested by the binding energy of the compound with receptor protein,Log SI,log P data and IC₅₀results.Results:1.Virtual docking showed that all 26 compounds interacted with HIV-1 proteins gp120,gp41 and spike and most of the compounds interacts with gp120 more strongly than with gp41 and spike.2.Cell experiments showed that three of these compounds had no toxicity to cells,which were MHW3,OHW2,OHW3;four of these compounds had less toxicity to cells,which ware MBW1,MEW3,MHW2,OBW1.3.Five of these compounds had obvious inhibitory effect on HIV-1,which were MBW1,OBW1,MEW3 and OHW2;4.Data of effective groups screened by software are in good agreement with the results of biological activity verification.5.The biological activity results of each molecule in vitro are not completely consistent with those of computer simulation docking.Conclusion:MHW1,MBW1,OBW1,MEW3 and OHW2 inhibit HIV-1 in low concentration,and the concentration of anti-HIV-1 activity reaches the micro-molar level,especially the antiviral effect of MHW1,is similar to that of T-20.MHW1is supposed to be a candidate drug for AIDS treatment.