Synthesis, Characterization, DFT Analysis, Pharmacokinetics, and Inhibition of Mpro and RdRp of SARS-CoV-2 by Two Dihydropyrimidines Derivatives

Abstract

In this work, two dihydropyrimidines derivatives: Ethyl 4-(2-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (2-DHPM) and Ethyl 4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (4-DHPM), were produced by a multi-component process, whose the yields were 83% and 90% respectively. FT-IR, UV-Vis, melting point, and NMR spectroscopy techniques were used to determine the structures of the two substances. Also, the density functional theory (DFT) was employed to discuss the reactivity of the created molecules as well as some parameters, including the energies of the frontier molecular orbitals (HOMO and LUMO), the dipole moment(µ), the energy gap ΔEgap (E_LUMO-E_HOMO), the global hardness (η), the global softness (σ), the absolute electronegativity (χ), and the electrophilicity index (ω). Also, predicted ADME-T were performed and the obtained parameters indicated that the compounds under investigation should have good oral bioavailability. Additionally, in silico docking was used to evaluate the studied derivative's inhibitory activity for the SARS-CoV-2 main protease (Mpro) and RNA dependent RNA polymerase (RdRp). These discoveries might open the door for the creation and evaluation of brand-new SARS-CoV-2 treatments.