Abstract
This study was designed to synthesize hybridizing molecules from ciprofloxacin and norfloxacin by enhancing their biological activity with tetrazoles. The synthesized compounds were investigated in the interaction with the target enzyme of fluoroquinolones (DNA gyrase) and COVID-19 main protease using molecular similarity, molecular docking, and QSAR studies. A QSAR study was carried out to explore the antibacterial activity of our compounds over Staphylococcus aureus a QSAR study, using descriptors obtained from the docking with DNA gyrase, in combination with steric type descriptors, was done obtaining suitable statistical parameters ( R2=87.00R2=87.00<math> <mrow><msup><mi>R</mi> <mn>2</mn></msup> <mo>=</mo> <mn>87.00</mn></mrow> </math> , Q2LMO=71.67QLMO2=71.67<math> <mrow><msubsup><mi>Q</mi> <mrow><mi>L</mi> <mi>M</mi> <mi>O</mi></mrow> <mn>2</mn></msubsup> <mo>=</mo> <mn>71.67</mn></mrow> </math> , and Q2EXT=73.49QEXT2=73.49<math> <mrow><msubsup><mi>Q</mi> <mrow><mi>E</mi> <mi>X</mi> <mi>T</mi></mrow> <mn>2</mn></msubsup> <mo>=</mo> <mn>73.49</mn></mrow> </math> ) to support our results. The binding interaction of our compounds with CoV-2-Mpro was done by molecular docking and were compared with different covalent and non-covalent inhibitors of this enzyme. For the docking studies we used several crystallographic structures of the CoV-2-Mpro. The interaction energy values and binding mode with several key residues, by our compounds, support the capability of them to be CoV-2-Mpro inhibitors. The characterization of the compounds was completed using FT-IR, 1H-NMR, 13C-NMR, 19F-NMR and HRMS spectroscopic methods. The results showed that compounds 1, 4, 5, 10 and 12 had the potential to be further studied as new antibacterial and antiviral compounds.