Computational Modeling Analysis and Retrosynthesis of Indole-Glyoxamide Derivatives as Potential HIV-1 Binding Inhibitors.

The current study uses computational 3D-QSAR, molecular docking, and molecular dynamics (MD) simulation approaches to examine the inhibitory effect of indole-glyoxamide-based drugs against HIV. The 3D-QSAR models were created using CoMFA and CoMSIA approaches, resulting in Q2=0.689, R2=0.933, and SEE=0.508. The CoMSIA model demonstrated strong molecule prediction, with a significant coefficient of determination R2test=0.932. The molecular docking and molecular dynamics simulations identified the binding mechanism and stability of the inhibitors under research. Additionally, we proposed five additional compounds (T2-T6) with much better inhibitory action based on the data retained by the CoMSIA contour maps. Additionally, the 3D-QSAR results were supported by molecular docking and MD simulation analyses, which supported the proposed compounds' stability in the receptor (PDB code: 1SJ0). The chosen compounds also exhibited acceptable pharmacokinetic characteristics and were non-toxic.