title: Synthesis, structure and cytotoxic activity of new acetylenic derivatives of betulin.
abstract: A new series of betulin derivatives containing one or two pharmacophores bearing an acetylenic and carbonyl function at the C-3 and/or C-28 positions has been synthesized and characterized by ¹H- and ¹³C-NMR, IR, MS and elemental analyses. The crystal structure of 28-O-propynoylbetulin was determined by X-ray structural analysis. All new compounds, as well as betulin, were tested in vitro for their antiproliferative activity against human SW707 colorectal, CCRF/CEM leukemia, T47D breast cancer, and against murine P388 leukemia and Balb3T3 normal fibroblasts cell lines. Most of the compounds showed better cytotoxicity than betulin and cisplatin used as reference agent. 28-O-Propynoylbetulin was the most potent derivative, being over 500 times more potent than betulin and about 100 times more cytotoxic than cisplatin against the human leukemia (CCRF/CEM) cell line, with an ID₅₀ value of 0.02 μg/mL.
authors.affiliation: Department of Organic Chemistry, Medical University of Silesia, 4 Jagiellonska Str., 41-200 Sosnowiec, Poland. boryczka@sum.edu.pl
authors.forename: Stanisław
authors.initials: S
authors.lastname: Boryczka
authors.forename: Ewa
authors.initials: E
authors.lastname: Bębenek
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kempińska
authors.forename: Maria
authors.initials: M
authors.lastname: Jastrzębska
authors.forename: Joachim
authors.initials: J
authors.lastname: Kusz
authors.forename: Maria
authors.initials: M
authors.lastname: Nowak
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D041702:BALB 3T3 Cells; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D006801:Humans; D007941:Leukemia P388; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid