Cu(II)-Catalyzed\nSynthesis of Pyrazolo[3,4‑<i>b</i>]pyridine Derivatives\nand Their Potential Antibacterial\nand Cytotoxic Activities with Molecular Docking, DFT Calculation,\nand SwissADME Analysis

The present work focuses on a newly synthesized pyrazolo[3,4-<i>b</i>]pyridine prepared by formal [3 + 3] cycloaddition using\ncopper(II) acetylacetonate as the catalyst; efficient and effective\nmild reactions with high yields were obtained using this method. The\nsynthesized compounds were identified by FT-IR, <sup>1</sup>H and <sup>13</sup>C NMR, and mass spectra (<i>m</i>/<i>z</i>) analyses. The compounds (<b>2a–l</b>) were screened\nfor several in vitro and in silico activities. Compound <b>2g</b> showed impressive inhibitory activities against methicillin-resistant Staphylococcus aureus (MIC: 2 μg/mL), vancomycin-resistant\nEnterococci (MIC: 8 μg/mL), piperacillin-resistant Pseudomonas aeruginosa, and extended-spectrum beta-lactamase-producing Escherichia coli (MIC: 4 μg/mL) compared to\nthe positive control, ciprofloxacin. Compared to standard doxorubicin,\ncompound <b>2g</b> had a higher efficacy against the HepG2 cancer\ncell line, with a GI<sub>50</sub> value of 0.01 μM. The highly\nactive compound <b>2g</b> was investigated for in silico molecular\ndocking, density functional theory calculations (DFT), and SwissADME\nphysicochemical properties. Compound <b>2g</b> had a higher\ndocking score compared with standard (−8.5 vs −7.3 and\n−10.0 vs −8.4 kcal/mol). In compound <b>2g</b>, the energy gap was 0.17 eV, as determined by using DFT calculations.\nThe physicochemical properties of all compounds were investigated\nby using SwissADME. Overall, compound <b>2g</b> exhibited promising\nantibacterial and cytotoxic activities.