Olexander M. Semenenko , Victoria V. Lipson , Alina O. Sadchenko , Olga V. Vashchenko , Natalia A. Kasian , Liliia V. Sviechnikova , Longin M. Lisetski , Mykola L. Babak , Volodymyr M. Vakula , Oleksandr V. Borysov , Yuliia V. Holota , Sergey O. Zozulya , Petro O. Borysko , Olexander V. Mazepa
{"title":"甲氨蝶呤-槟榔酸杂化物的合成及其对人工和Caco-2细胞膜的影响评价。","authors":"Olexander M. Semenenko , Victoria V. Lipson , Alina O. Sadchenko , Olga V. Vashchenko , Natalia A. Kasian , Liliia V. Sviechnikova , Longin M. Lisetski , Mykola L. Babak , Volodymyr M. Vakula , Oleksandr V. Borysov , Yuliia V. Holota , Sergey O. Zozulya , Petro O. Borysko , Olexander V. Mazepa","doi":"10.1016/j.steroids.2023.109332","DOIUrl":null,"url":null,"abstract":"<div><p>An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids with a (<em>tert</em>-butoxycarbonylamino)-3,6-dioxa-8-octanamine (<em>Boc</em>-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 <sup>1</sup>H NMR, <sup>13</sup>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.</p></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":null,"pages":null},"PeriodicalIF":2.1000,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis of methotrexate-betulonic acid hybrids and evaluation of their effect on artificial and Caco-2 cell membranes\",\"authors\":\"Olexander M. Semenenko , Victoria V. Lipson , Alina O. Sadchenko , Olga V. Vashchenko , Natalia A. Kasian , Liliia V. Sviechnikova , Longin M. Lisetski , Mykola L. Babak , Volodymyr M. Vakula , Oleksandr V. Borysov , Yuliia V. Holota , Sergey O. Zozulya , Petro O. Borysko , Olexander V. Mazepa\",\"doi\":\"10.1016/j.steroids.2023.109332\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>An efficient protocol for the synthesis of novel methotrexate-betulonic acid hybrids with a (<em>tert</em>-butoxycarbonylamino)-3,6-dioxa-8-octanamine (<em>Boc</em>-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 <sup>1</sup>H NMR, <sup>13</sup>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.</p></div>\",\"PeriodicalId\":21997,\"journal\":{\"name\":\"Steroids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2023-11-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Steroids\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0039128X23001605\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Steroids","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0039128X23001605","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Synthesis of methotrexate-betulonic acid hybrids and evaluation of their effect on artificial and Caco-2 cell membranes
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.
期刊介绍：
STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.
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