title: New insights into the structure-cytotoxicity relationship of spirostan saponins and related glycosides.
abstract: A variety of spirostan saponins and related glycosides were synthesized and evaluated for their cytotoxicity against the human myeloid leukemia cell line (HL-60). A linear glycosylation strategy allowed for accessing a variety of functionalization patterns at both the spirostanic and the saccharide moieties, which provides new information regarding the structure-cytotoxicity relationship of this family of steroidal glycosides. Intriguing results were achieved with respect to hecogenyl and 5α-hydroxy-laxogenyl β-chacotriosides, turning out to be the former very cytotoxic and the latter no cytotoxic at all. Importantly, the partially pivaloylated β-d-glucosides of 5α-hydroxy-laxogenin were the most potent cytotoxic compounds among all tested glycosides. This comprises the first report on acylated spirostanyl glucosides displaying significant cytotoxicity, and therefore, it opens up new opportunities toward the development of saponin analogues as anticancer agents.
authors.affiliation: Instituto de Productos Naturales y Agrobiología-CSIC, Av. Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain.
authors.forename: Karell
authors.initials: K
authors.lastname: Pérez-Labrada
authors.forename: Ignacio
authors.initials: I
authors.lastname: Brouard
authors.forename: Sara
authors.initials: S
authors.lastname: Estévez
authors.forename: María Teresa
authors.initials: MT
authors.lastname: Marrero
authors.forename: Francisco
authors.initials: F
authors.lastname: Estévez
authors.forename: Jaime
authors.initials: J
authors.lastname: Bermejo
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Rivera
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018922:HL-60 Cells; D006801:Humans; D008968:Molecular Conformation; D012503:Saponins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013150:Spirostans / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D006027:Glycosides; D012503:Saponins; D013150:Spirostans