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

İNCE T., SERTTAŞ R., DEMİR B., Atabey H., SEFEROĞLU N., ERDOGAN S., ...Daha Fazla

JOURNAL OF MOLECULAR STRUCTURE, cilt.1217, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1217
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.molstruc.2020.128400
  • Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Chimica, Compendex, INSPEC
  • Anahtar Kelimeler: Triazole, Pyrrolidine, Click chemistry, Acid dissociation constant, Anticancer activity, DFT, STEM-CELL SURVIVAL, BIOLOGICAL EVALUATION, PROSTATE-CANCER, ANTIMICROBIAL ACTIVITY, MOLECULAR-STRUCTURE, CLICK CHEMISTRY, ANTICANCER, DERIVATIVES, INHIBITION, DISCOVERY
  • Gazi Üniversitesi Adresli: Evet

Özet

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 in excellent 89-95% yield. The H-1 NMR, C-13 NMR, DEPT, COSY, HMQC, FT-IR, HRMS and elemental analysis techniques were used for structural characterization. A single crystal X-ray diffraction study was performed in order to determine the stereochemistry of the compounds. The optimization geometry of the compounds was obtained by performing density functional theory. However, the global reactivity parameters were estimated from frontier molecular orbitals. The calculated global reactivity parameters showed that the most reactive compound was 4e and the least reactive compounds were 4a, 4c and 4d. The acid dissociation constants were determined using potentiometric titration in 20% (v/v) dimethyl sulfoxide-water hydro-organic solvent at 25 +/- 0.1 degrees C, and four dissociation constants relating nitrogen atoms were obtained for each ligand. Six synthesized compounds were screened for their in vitro anti-proliferative activities against human prostate cancer cells, all of which significantly reduced cell proliferation. One of the compounds 4d showed much more anti-proliferative potential relative to the others, delaying the cells at the DNA synthesis phase. The drug-likeness model score (DLS) calculations for all the synthesized compounds using MolSoft websites supported the experimental results of anti-proliferative bioactivity study, and 4d was found to be maximum DLS value of 1.01. (C) 2020 Elsevier B.V. All rights reserved.