Synthesis of oxazolidinone from enantiomerically enriched allylic alcohols and determination of their molecular docking and biologic activities

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Atmaca U., Kaya R., Karaman H. S., Çelik M., Gülçin İ.

BIOORGANIC CHEMISTRY, cilt.88, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 88
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.bioorg.2019.102980
  • Dergi Adı: BIOORGANIC CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Anahtar Kelimeler: Enantiomerically enriched, Allylic alcohols, Carbonic anhydrase, alpha-Glycosidase, Acetylcholinesterase, Molecular docking, ANHYDRASE INHIBITORY PROPERTIES, POTENT CARBONIC-ANHYDRASE, ISOENZYMES I, ANTICHOLINERGIC ACTIVITIES, CRYSTAL-STRUCTURE, 1ST SYNTHESIS, HCA I, ACETYLCHOLINESTERASE, DERIVATIVES, ANTIOXIDANT
  • Atatürk Üniversitesi Adresli: Evet

Özet

Enantioselective synthesis of functionalized cyclic allylic alcohols via kinetic resolution in transesterifcation with different lipase enzymes has been developed. The influence of the enzymes and temperature activity was studied. By determination of ideal reaction conditions, byproduct formation is minimized; this made it possible to prepare enantiomerically enriched allylic alcohols in high ee's and good yields. Enantiomerically enriched allylic alcohols were used for enantiomerically enriched oxazolidinone synthesis. Using benzoate as a leaving group means that 1 mol % of potassium osmate is necessary and can be obtained high yields 98%. Inhibitory activities of enantiomerically enriched oxazolidinones (8, 10 and 12) were tested against human carbonic anhydrase I and II isoenzymes (hCA I and hCA II), acetylcholinesterase (AChE), and alpha-glycosidase (alpha-Gly) enzymes. These enantiomerically enriched oxazolidinones derivatives had K-i values in the range of 11.6 +/- 2.1-66.4 +/- 22.7 nM for hCA I, 34.1 +/- 6.7-45.2 +/- 12.9 nM for hCA II, 16.5 +/- 2.9 to 35.6 +/- 13.9 for AChE, and 22.3 +/- 6.0-70.9 +/- 9.9 nM for alpha-glycosidase enzyme. Moreover, they had high binding affinity with -5.767, -6.568, -9.014, and -8.563 kcal/mol for hCA I, hCA II, AChE and alpha-glycosidase enzyme, respectively. These results strongly supported the promising nature of the enantiomerically enriched oxazolidinones as selective hCA, AChE, and alpha-glycosidase inhibitors. Overall, due to these derivatives' inhibitory potential on the tested enzymes, they are promising drug candidates for the treatment of diseases like glaucoma, leukemia, epilepsy; Alzheimer's disease; type-2 diabetes mellitus that are associated with high enzymatic activity of CA, AChE, and alpha-glycosidase.