Pd-catalyzed synthesis, characterization, and biological evaluations of pyrazole derivatives: DFT, molecular modelling and antioxidant studies

Abstract

Using Pd(PPh3)4 as a catalyst, a new series of coupling products (5a–5l) synthesized from pyrazole derivatives (4a-4c) and substituted boronic acids. Afterward, 1H, 13C-NMR, FT-IR, UV-visible, and LC-MS techniques were used to characterize the pyrazole derivatives. These pyrazole derivatives (4a-4c and 5a-5l) were assessed for their in-vitro antifungal activity, growth pattern evaluations, and hemolytic assays against the Candida strains. The antibacterial inhibitory potential of the lead compound 5c, with a panel of three Gram-positive bacterial strains and two Gram-negative bacterial strains, was employed to find out MIC, FICI, and toxicity. Results showed that the MIC values with all bacterial strains for compound 5c indicate substantial antimicrobial potential. Analog 5c was tested for its ability to interact with Ct-DNA using various techniques. Compound 5c showed binding constants (Kb) of 9.93 × 105 M−1 while the Gibbs free energy was -34.22 kJmol−1. The linear Stern-Volmer constant (KSV) for 5c was calculated to be 4.81 × 104. DFT calculation study has been investigated for the geometrical optimization and energy parameters calculation. Pyrazole derivative 5c was used for molecular modelling investigation with PDB: 1BNA, 2XCT, and 5FSA, which validated the manner of binding and supported in vitro DNA binding results. Utilizing the DPPH and H2O2 assay, derivative 5c was also tested for antioxidant activity.