Modified Thymidine Derivatives as Potential Inhibitors of SARS-CoV: PASS, In Vitro Antimicrobial, Physicochemical and Molecular Docking Studies

Thymidine and thymidine-mimicking derivatives were found promising against microorganisms which may inhibit the growth of microorganisms providing effective therapies for several diseases. In this present study, it has been investigated the antimicrobial activities of thymidine and some of its designed derivatives by employing quantum chemical calculations. The antimicrobial tests demonstrated that the compounds 3, 4, and 14 were the most active against Pseudomonas aeruginosa, Salmonella abony, and Staphylococcus aureus strains, with the calculated MIC values ranging from 0.32 ± 0.01 to 1.25 ± 0.03 mg ml-1 and MBC values ranging from 0.32±0.01 to 2.5±0.06 mg ml-1. These derivatives exhibited much stronger biochemical activities than the standard antibacterial drugs. SAR study including in vitro and in silico analysis revealed that the lauroyl and myristoyl in combination with ribose sugar were found to be the most potential activates. PASS and quantum calculations respectively revealed excellent antimicrobial and thermodynamic properties of the designed thymidine derivatives. A molecular docking study has been performed against SARS-CoV main protease protein to investigate their binding energies and binding modes and observed that, designed derivatives exhibited improved binding affinities. In addition, the ADMET studies predicted the pharmacokinetic properties with lower acute oral toxicity i.e, noncarcinogenic of all compounds.