Polysubstituted pyrrolidines linked to 1,2,3-triazoles: Synthesis, crystal structure, DFT studies, acid dissociation constant, drug-likeness, and anti-proliferative activity

摘要: Abstract Novel pyrrolidines linked to 1,2,3-triazole derivatives, dimethyl 1-(2-(4-R-1H-1,2,3-triazol-1-yl)acetyl)-5,5-diphenylpyrrolidine-2,4-dicarboxylate, were synthesized in the presence of sodium ascorbate and copper (II) sulfate pentahydrate by click chemistry excellent 89–95% yield. The 1H NMR, 13C DEPT, COSY, HMQC, FT-IR, HRMS elemental analysis techniques used for structural characterization. A single crystal X-ray diffraction study was performed order determine stereochemistry compounds. optimization geometry compounds obtained performing density functional theory. However, global reactivity parameters estimated from frontier molecular orbitals. calculated showed that most reactive compound 4e least 4a, 4c 4d. acid dissociation constants determined using potentiometric titration 20% (v/v) sulfoxide-water hydro-organic solvent at 25 ± 0.1 °C, four relating nitrogen atoms each ligand. Six screened their in vitro anti-proliferative activities against human prostate cancer cells, all which significantly reduced cell proliferation. One 4d much more potential relative others, delaying cells DNA synthesis phase. drug-likeness model score (DLS) calculations MolSoft websites supported experimental results bioactivity study, found be maximum DLS value 1.01.