Chemoenzymatic synthesis of enantiomeric, bicyclic δ-halo-γ-lactones with a cyclohexane ring, their biological activity and interaction with biological membranes
Marcelina Mazur , Aleksandra Włoch , Fouad Bahri , Hanna Pruchnik , Aleksandra Pawlak , Bożena Obmińska-Mrukowicz , Gabriela Maciejewska , Witold Gładkowski
AbstractStarting from 1-acetyl-1-cyclohexene, three enantiomeric pairs (ee ≥ 99%) of bicyclic δ-halo-γ-lactones with cyclohexane ring were obtained in five-step synthesis. The key stereochemical steps were lipase-catalyzed kinetic resolution of racemic 1-(cyclohex-1-en-1-yl) ethanol followed by transfer of chirality to ethyl 2-(2-ethylidenecyclohexyl) acetate in the Johnson–Claisen rearrangement. Synthesized halolactones exhibited antiproliferative activity towards canine B-cell leukemia cells (GL-1) and canine B-cell chronic leukemia cells (CLB70) and the most potent (IC50 18.43 ± 1.46 μg/mL against GL-1, IC50 11.40 ± 0.40 μg/mL against CLB70) comparable with the control etoposide, was (1R,6R,1′S)-1-(1′-chloroethyl)-9-oxabicyclo[4.3.0]nonan-8-one (8b). All halolactones did not have a toxic effect on erythrocytes and did not change the fluidity of membranes in the hydrophobic region of the lipid bilayer. Only weak changes in the hydrophilic area were observed, like the degree of lipid packing and associated hydration. The racemic halolactones were also tested for their antimicrobial properties and found to exhibit selectivity towards bacteria, in particular, towards Proteus mirabilis ATCC 35659.
|Journal series||Biomolecules, ISSN 2218-273X, e-ISSN 2218-273X, (N/A 100 pkt)|
|Publication size in sheets||0.85|
|Keywords in English||lactones; halolactonisation; kinetic resolution ofalcohols; antimicrobial activity; antiproliferative activity; hemolytic activity; erythrocytes; biological membranes|
|Internal identifier||PX-5e413c02d5de44d25e175eea; PX-5e413eacd5de44d25e175ef9; PX-5e4140b4d5de44d25e175f12|
|License||Journal (articles only); published final; ; with publication|
|Score||= 100.0, 28-04-2021, ArticleFromJournal|
|Publication indicators||= 2; = 2; : 2018 = 1.641; : 2018 = 4.694 (2)|
|Citation count*||2 (2021-05-09)|
* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.