title: Solid-phase library synthesis of bi-functional derivatives of oleanolic and maslinic acids and their cytotoxicity on three cancer cell lines.
abstract: A wide set of 264 compounds has been semisynthesized with high yields and purities. These compounds have been obtained through easy synthetic processes based on a solid-phase combinatorial methodology. All the members of this library have one central core of a natural pentacyclic triterpene (oleanolic or maslinic acid) and differ by 6 amino acids, coupled with the carboxyl group at C-28 of the triterpenoid skeleton, and by 10 different acyl groups attached to the hydroxyl groups of the A-ring of these molecules. According to the literature on the outstanding and promising pharmacological activities of other similar terpene derivatives, some of these compounds have been tested for their cytotoxic effects on the proliferation of three cancer cell lines: B16-F10, HT29, and Hep G2. In general, we have found that around 70% of the compounds tested show cytotoxicity in all three of the cell lines selected; around 60% of the cytotoxic compounds are more effective than their corresponding precursors, that is, oleanolic (OA) or maslinic (MA) acids; and nearly 50% of the cytotoxic derivatives have IC50 values between 2- to 320-fold lower than their corresponding precursor (OA or MA).
authors.affiliation: Departamento de Quimica Organica, Facultad de Ciencias, Universidad de Granada , E-18071 Granada, Spain.
authors.forename: Andres
authors.initials: A
authors.lastname: Parra
authors.forename: Samuel
authors.initials: S
authors.lastname: Martin-Fonseca
authors.forename: Francisco
authors.initials: F
authors.lastname: Rivas
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Reyes-Zurita
authors.forename: Marta
authors.initials: M
authors.lastname: Medina-O'Donnell
authors.forename: Eva E
authors.initials: EE
authors.lastname: Rufino-Palomares
authors.forename: Antonio
authors.initials: A
authors.lastname: Martinez
authors.forename: Andres
authors.initials: A
authors.lastname: Garcia-Granados
authors.forename: Jose A
authors.initials: JA
authors.lastname: Lupiañez
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
mesh_terms: D000215:Acylation; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D020650:Combinatorial Chemistry Techniques; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D009828:Oleanolic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000031:analogs & derivatives; D060327:Solid-Phase Synthesis Techniques; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; D009828:Oleanolic Acid; C412811:maslinic acid