{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T21:49:22Z","timestamp":1790200162533,"version":"4.1.0"},"reference-count":30,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004578","name":"Ministerstvo Pr\u016fmyslu a Obchodu","doi-asserted-by":"publisher","award":["FV10599"],"award-info":[{"award-number":["FV10599"]}],"id":[{"id":"10.13039\/501100004578","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004578","name":"Ministerstvo Pr\u016fmyslu a Obchodu","doi-asserted-by":"publisher","award":["FV30300"],"award-info":[{"award-number":["FV30300"]}],"id":[{"id":"10.13039\/501100004578","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The target diosgenin\u2013betulinic acid conjugates are reported to investigate their ability to enhance and modify the pharmacological effects of their components. The detailed synthetic procedure that includes copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition (click reaction), and palladium-catalyzed debenzylation by hydrogenolysis is described together with the results of cytotoxicity screening tests. Palladium-catalyzed debenzylation reaction of benzyl ester intermediates was the key step in this synthetic procedure due to the simultaneous presence of a 1,4-disubstituted 1,2,3-triazole ring in the molecule that was a competing coordination site for the palladium catalyst. High pressure (130 kPa) palladium-catalyzed procedure represented a successful synthetic step yielding the required products. The conjugate 7 showed selective cytotoxicity in human T-lymphoblastic leukemia (CEM) cancer cells (IC50 = 6.5 \u00b1 1.1 \u00b5M), in contrast to the conjugate 8 showing no cytotoxicity, and diosgenin (1), an adaptogen, for which a potential to be active on central nervous system was calculated in silico. In addition, 5 showed medium multifarious cytotoxicity in human T-lymphoblastic leukemia (CEM), human cervical cancer (HeLa), and human colon cancer (HCT 116). Betulinic acid (2) and the intermediates 3 and 4 showed no cytotoxicity in the tested cancer cell lines. The experimental data obtained are supplemented by and compared with the in silico calculated physico-chemical and absorption, distribution, metabolism, and excretion (ADME) parameters of these compounds.<\/jats:p>","DOI":"10.3390\/molecules25153546","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T05:56:46Z","timestamp":1596520606000},"page":"3546","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Synthesis and Pharmacological Effects of Diosgenin\u2013Betulinic Acid Conjugates"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9083-4919","authenticated-orcid":false,"given":"Z\u00fclal","family":"\u00d6zdemir","sequence":"first","affiliation":[{"name":"Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"},{"name":"Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technick\u00e1 5, 16628 Prague 6, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Rybkov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technick\u00e1 5, 16628 Prague 6, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1044-1910","authenticated-orcid":false,"given":"Martin","family":"Vlk","sequence":"additional","affiliation":[{"name":"Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"},{"name":"Faculty of Nuclear Sciences and Physical Engineering, Czech Technical University in Prague, B\u0159ehov\u00e1 7, 11519 Prague 1, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"\u0160aman","sequence":"additional","affiliation":[{"name":"Department of NMR Spectroscopy, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo n\u00e1m\u011bst\u00ed 2, 16610 Prague 6, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucie","family":"R\u00e1rov\u00e1","sequence":"additional","affiliation":[{"name":"Laboratory of Growth Regulators, Faculty of Science, Palack\u00fd University, and Institute of Experimental Botany of the Czech Academy of Sciences, \u0160lechtitel\u016f 27, 78371 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zden\u011bk","family":"Wimmer","sequence":"additional","affiliation":[{"name":"Isotope Laboratory, Institute of Experimental Botany of the Czech Academy of Sciences, V\u00edde\u0148sk\u00e1 1083, 14220 Prague 4, Czech Republic"},{"name":"Department of Chemistry of Natural Compounds, University of Chemistry and Technology in Prague, Technick\u00e1 5, 16628 Prague 6, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1016\/j.phymed.2014.06.009","article-title":"Bergenia crassifolia (L.) 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