Synthesis of methotrexate-betulonic acid hybrids and evaluation of their effect on artificial and Caco-2 cell membranes.

Autor: Semenenko OM; Department of Organic and Bioorganic Chemistry, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Lipson VV; Department of Organic and Bioorganic Chemistry, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine; Medicinal Chemistry Department, State Institution 'V.Ya. Danilevsky Institute for Endocrine Pathology Problems' NAMS of Ukraine, Alchevskih St., 10, 61002 Kharkiv, Ukraine; Organic Chemistry Department, V.N. Karazin Kharkiv National University, Svobody Sq., 4, 61022 Kharkiv, Ukraine. Electronic address: lipson@ukr.net., Sadchenko AO; Institute for Scintillation Materials, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Vashchenko OV; Institute for Scintillation Materials, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Kasian NA; Institute for Scintillation Materials, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Sviechnikova LV; Institute for Scintillation Materials, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Lisetski LM; Institute for Scintillation Materials, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Babak ML; Department of Organic and Bioorganic Chemistry, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine., Vakula VM; Department of Organic and Bioorganic Chemistry, State Scientific Institution 'Institute for Single Crystals' NAS of Ukraine, Nauky Ave., 60, 61072 Kharkiv, Ukraine; Medicinal Chemistry Department, State Institution 'V.Ya. Danilevsky Institute for Endocrine Pathology Problems' NAMS of Ukraine, Alchevskih St., 10, 61002 Kharkiv, Ukraine., Borysov OV; Enamine Ltd., 23 Chervonotkatska str., 01003 Kyiv, Ukraine., Holota YV; Enamine Ltd., 23 Chervonotkatska str., 01003 Kyiv, Ukraine., Zozulya SO; Enamine Ltd., 23 Chervonotkatska str., 01003 Kyiv, Ukraine., Borysko PO; Enamine Ltd., 23 Chervonotkatska str., 01003 Kyiv, Ukraine., Mazepa OV; A. V. Bogatsky Physico-Chemical Institute NAS of Ukraine, Lustdorfska Road, 86, 65080 Odesa, Ukraine.
Jazyk: angličtina
Zdroj: Steroids [Steroids] 2024 Jan; Vol. 201, pp. 109332. Date of Electronic Publication: 2023 Nov 07.
DOI: 10.1016/j.steroids.2023.109332
Abstrakt: 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 1 H NMR, 13 C 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.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2023. Published by Elsevier Inc.)
Databáze: MEDLINE
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