title: Synthesis and cytotoxic activity of new betulin and betulinic acid esters with conjugated linoleic acid (CLA).
abstract: The synthesis of new ester derivatives of betulin (3a-c) and betulinic acid (4) with conjugated linoleic acid isomers (CLA; in a mixture of 43.4% 9c, 11t; 49.5% 10t, 12c; 7.1% other isomers) is presented. Esterification was carried out with N,N'-dicyclohexylcarbodiimide (DCC) as the coupling agent in the presence of 4-dimethylamino-pyridine (DMAP) in dichloromethane (or pyridine). The in vitro cytotoxic effect of betulin (1), betulinic acid (2), a mixture of CLA isomers and their derivatives (3a-c, 4) was examined using the MTT assay against four cancer cell lines (P388, CEM/C2, CCRF/CEM and HL-60) and the SRB assay on the HT-29 cell line. Ester 4 was the most active among the esters synthesized against the CEM/C2 cell line with an ID50 value 16.9 +/- 6.5 microg/mL. Betulin (1), betulinic acid (2) and CLA were the most active agents against the cancer cell lines studied.
authors.affiliation: Department of Chemistry, Faculty of Food Sciences, Wrocław University of Environmental and Life Sciences, Norwida 25, 50-375 Wrocław, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Tubek
authors.forename: Paweł
authors.initials: P
authors.lastname: Mituła
authors.forename: Natalia
authors.initials: N
authors.lastname: Niezgoda
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kempińska
authors.forename: Joanna
authors.initials: J
authors.lastname: Wietrzyk
authors.forename: Czesław
authors.initials: C
authors.lastname: Wawrzeńczyk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D044243:Linoleic Acids, Conjugated; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid