title: Derivatives of grindelic acid: from a non-active natural diterpene to synthetic antitumor derivatives.
abstract: Using several reactions that include homologations and asymmetric epoxidations as well as Ugi and Huisgen couplings, we generated a small focused library of new derivatives from the labdane-type diterpene grindelic acid. These compounds were evaluated as cytotoxic agents against a panel of five human solid tumor cell lines (HBL-100, HeLa, SW1573, T-47D, and WiDr). The presence of the diamide functionalizations enhanced the cytotoxic effect. N-Benzyl-N-(1-(benzylamino)-2-methyl-1-oxopropan-2-yl)grindelicamide, proved to be the most active product in all cell lines tested, with values of 0.95 (±0.38) μM against HBL-100 cells.
authors.affiliation: INTEQUI-CONICET, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco y Pedernera, 5700 San Luis, Argentina.
authors.forename: Guillermo F
authors.initials: GF
authors.lastname: Reta
authors.forename: Alejandra I
authors.initials: AI
authors.lastname: Chiaramello
authors.forename: Celina
authors.initials: C
authors.lastname: García
authors.forename: Leticia G
authors.initials: LG
authors.lastname: León
authors.forename: Víctor S
authors.initials: VS
authors.lastname: Martín
authors.forename: José M
authors.initials: JM
authors.lastname: Padrón
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Tonn
authors.forename: Osvaldo J
authors.initials: OJ
authors.lastname: Donadel
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D004224:Diterpenes; C587475:grindelic acid
keywords: 1,2,3-Triazole; Antitumor activity; Diamide derivatives; Labdane-type diterpenes; Multicomponent reactions