title: Novel semisynthetic derivatives of betulin and betulinic acid with cytotoxic activity.
abstract: A series of new imidazole carboxylic esters (carbamates) and N-acylimidazole derivatives of betulin and betulinic acid (14-29) have been synthesized. The new compounds were screened for in vitro cytotoxicity activity against human cancer cell lines HepG2, Jurkat and HeLa. A number of compounds have shown IC(50) values lower than 2 microM against the cancer cell lines tested and the vast majority has shown a better cytotoxicity profile than betulinic acid, including the betulin derivatives. N-Acylimidazole derivatives 26 and 27 (IC(50) 0.8 and 1.7 microM in HepG2 cells) and the C-3 carbamate derivative 16 (IC(50) 2.0 microM in HepG2 cells) were the most promising compounds. Based on the observed cytotoxicity, structure-activity relationships have been established.
authors.affiliation: Laboratório de Química Farmacêutica, Faculdade de Farmácia, Universidade de Coimbra, Polo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Rita C
authors.initials: RC
authors.lastname: Santos
authors.forename: Jorge A R
authors.initials: JA
authors.lastname: Salvador
authors.forename: Silvia
authors.initials: S
authors.lastname: Marín
authors.forename: Marta
authors.initials: M
authors.lastname: Cascante
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D053978:Pentacyclic Triterpenes; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid