1. Synthesis of methotrexate-betulonic acid hybrids and evaluation of their effect on artificial and Caco-2 cell membranes.
- Author
-
Semenenko, Olexander M., Lipson, Victoria V., Sadchenko, Alina O., Vashchenko, Olga V., Kasian, Natalia A., Sviechnikova, Liliia V., Lisetski, Longin M., Babak, Mykola L., Vakula, Volodymyr M., Borysov, Oleksandr V., Holota, Yuliia V., Zozulya, Sergey O., Borysko, Petro O., and Mazepa, Olexander V.
- Subjects
- *
ARTIFICIAL cells , *CELL membranes , *ARTIFICIAL membranes , *DIFFERENTIAL scanning calorimetry , *COLUMN chromatography - Abstract
[Display omitted] • Novel isomeric methotrexate-betulonic acid hybrids have been synthesized. • Experiments with artificial membranes confirmed high lipophilicity of hybrids. • The ability of the conjugates to penetrate Caco-2 cells has been evaluated. An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids with a (tert -butoxycarbonylamino)-3,6-dioxa-8-octanamine (Boc -DOOA) linkage has been developed. Reaction of N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-betulonamide with methotrexate resulted in a mixture of isomeric conjugates which were separated by column chromatography. Their structures and composition have been fully established by 1H NMR, 13C spectra, FAB mass spectrometry and elemental analysis. The identity of conjugates was confirmed by LC-MS data. Membranotropic properties of the new hybrids were assessed on the basis of their interactions with artificial lipid membranes by differential scanning calorimetry (DSC) method. The ability of the conjugates to penetrate Caco-2 cells is inferior to methotrexate. Probably, this is due to the increasing lipophilicity, the affinity of these hybrid molecules for the lipid bilayer increases, which is confirmed by experiments with artificial membranes. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF