Study on the Molecular Dynamics of 2-(4-Fluorophenyl)-6-methyl-4-(3- (trifluoromethyl)phenyl)-1,2-dihydrodipyrazolo[3,4-b:3′,4′- <i>d</i> ]pyridin-3(6 <i>H</i> )-one for Cancer Immunotherapy Using a DFT Model

Small-molecule inhibitors targeting the B7-CD28 pathway represent a promising strategy for cancer immunotherapy. This study presents a comprehensive in silico characterization of 2-(4-fluorophenyl)-6-methyl-4-(3-(trifluoromethyl)-phenyl)-1,2-dihydropyrazolo-[3,4-b:3',4'-<i>d</i>]-pyridin-3-(6<i>H</i>)-one to evaluate its potential as a dual-target inhibitor within the B7-CD28 pathway. Using density functional theory (DFT) at the B3LYP/6- 311G-(d) level, the molecule's structural and electronic properties were thoroughly characterized. Simulated spectroscopic profiles (Fourier transform infrared spectroscopy (FT-IR), Raman, and ultraviolet-visible (UV-Vis)) were generated, with vibrational modes validated through potential energy distribution (PED) analysis. Electronic characterizationincluding the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy gap, density of states (DOS), and topological descriptors such as the electron localization function (ELF), localized orbital locator (LOL), and reduced density gradient (RDG)highlighted features governing the molecule's reactivity and stability. Natural bond orbital (NBO) analysis quantified key hyperconjugative interactions (<i>E</i> ⁽²⁾) contributing to intramolecular stability, while local reactivity was further examined using Fukui functions. The ¹H and ¹³C NMR chemical shifts were predicted via the gauge-independent atomic orbital (GIAO) method. Molecular docking with AutoDock Vina revealed strong binding affinities toward CD80 (-7.54 kcal·mol^-1) and CTLA-4 (-7.97 kcal·mol^-1), suggesting effective inhibition of the B7-CD28/CTLA-4 signaling axis. Additionally, in silico ADMET analysis indicated favorable pharmacokinetic and absorption properties, supporting the compound's potential as a promising immunotherapeutic candidate.