RESUMEN
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 ( R 2 = 87.00 , Q L M O 2 = 71.67 , and Q E X T 2 = 73.49 ) 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.
RESUMEN
New fluorescent molecular probes, which can selectively target specific cell surface receptors, are needed for microscopy, in vivo imaging, and image guided surgery. The preparation of multivalent probes using standard synthetic chemistry can be a laborious process due to low reaction yields caused by steric effects. In this study, fluorescent molecular probes were prepared by a programmed non-covalent pre-assembly process that used a near-infrared fluorescent squaraine dye to thread a macrocycle bearing a cyclic arginine-glycine-aspartate peptide antagonist (cRGDfK) as a cancer targeting unit. Cell microscopy studies using OVCAR-4 (ovarian cancer) and A549 (lung cancer) cells that express high levels of the integrin αvß3 or αvß5 receptors, respectively, revealed a multivalent cell targeting effect. That is, there was comparatively more cell uptake of a pre-assembled probe equipped with two copies of the cRGDfK antagonist than a pre-assembled probe with only one appended cRGDfK antagonist. The remarkably high photostability and low phototoxicity of these near-infrared probes allowed for acquisition of long-term fluorescence movies showing endosome trafficking in living cells. In vivo near-infrared fluorescence imaging experiments compared the biodistribution of a targeted and untargeted probe in a xenograft mouse tumor model. The average tumor-to-muscle ratio for the pre-assembled targeted probe was 3.6 which matches the tumor targeting performance reported for analogous cRGDfK-based probes that were prepared entirely by covalent synthesis. The capability to excite these pre-assembled near-infrared fluorescent probes with blue or deep-red excitation light makes it possible to determine if a target site is located superficially or buried in tissue, a probe performance feature that is likely to be very helpful for eventual applications such as fluorescence guided surgery.