Design, Synthesis, QSAR and Molecular Docking of Substituted Chalcones as Selective COX-2 Inhibitors: A Review

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@article{1724050,
      author = {Anushka Yadav, Raj Kumar},
      title = {Design, Synthesis, QSAR and Molecular Docking of Substituted Chalcones as Selective COX-2 Inhibitors: A Review},
      journal = {Iconic Research And Engineering Journals},
      year = {2026},
      volume = {10},
      number = {4},
      pages = {2511-2522},
      issn = {2456-8880},
      url = {https://www.irejournals.com/formatedpaper/1724050.pdf},
      abstract = {Selective inhibition of the inducible cyclooxygenase-2 (COX-2) isoform, while sparing constitutive, gastroprotective COX-1, remains a central strategy for developing safer anti-inflammatory agents, and the chalcone scaffold, a chemically simple 1,3-diarylprop-2-en-1-one, has repeatedly proven amenable to the substituent patterning this selectivity requires. This review synthesises the rational design, synthesis and evaluation strategy proposed for a focused series of eight substituted chalcones (CH-1 to CH-8) built around a constant 4-(methylsulfonyl)phenyl ring-A, the same sulfone-based pharmacophore established in celecoxib, fused through an enone linker to a ring-B bearing eight substituents spanning a wide Hammett sigma range from strongly electron-donating (4-N(CH3)2, sigma -0.83) to strongly electron-withdrawing (4-NO2, sigma +0.78). The structural basis for COX-2 selectivity, centred on the Val523-for-Ile523 substitution that opens a second hydrophobic side pocket in COX-2 but not COX-1, is discussed alongside the base-catalysed Claisen-Schmidt condensation route proposed for the series, the full spectroscopic and chromatographic characterisation strategy, RDKit-computed physicochemical and Lipinski-rule profiling, AutoDock Vina-based molecular docking against the COX-2 crystal structure, in-vitro COX-1/COX-2 inhibition and selectivity-index determination, and a Hansch-type quantitative structure-activity relationship (QSAR) framework relating log(1/IC50) to Hammett sigma, calculated lipophilicity and topological polar surface area. Precedent from recent chalcone-COX-2 and chalcone-QSAR literature is drawn together to situate the proposed series, and in particular its combination of systematic electronic variation, parallel dual-isoform in-vitro screening, docking validation and Hansch-type QSAR modelling within a single internally consistent study, against the wider body of chalcone-based cyclooxygenase inhibitor design.},
      keywords = {chalcones; cyclooxygenase-2; selective COX-2 inhibitors; Claisen-Schmidt condensation; Hammett sigma; molecular docking; Hansch QSAR; celecoxib},
      month = {October},
  }