title: Discovery of Mandelalide E and Determinants of Cytotoxicity for the Mandelalide Series.
abstract: Recollection of the tunicate source of the mandelalides has provided new and known analogues that have facilitated expanded analyses of the disputed cancer cytotoxicity of mandelalide A following a number of recent reported total syntheses. Using newly characterized mandelalide E, reisolated natural mandelalides B and C, and synthetic mandelalide A, the cytotoxicity of the mandelalides is demonstrated to be strongly influenced by compound glycosylation and assay cell density. Glycosylated mandelalides reduced the viability of human cancer cells cultured at a high starting density with a rank order of potency A > B ≫ E, yet display dramatically reduced cytotoxic efficacy against low density cultures.
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , 203 Pharmacy Building, Corvallis, Oregon 97331-4003, United States.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Nazari
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , 203 Pharmacy Building, Corvallis, Oregon 97331-4003, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Serrill
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , 203 Pharmacy Building, Corvallis, Oregon 97331-4003, United States.
authors.forename: Justyna
authors.initials: J
authors.lastname: Sikorska
authors.affiliation: Laboratory of Chemical Genomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School Xili , Nanshan District, Shenzhen 518055, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Ye
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , 203 Pharmacy Building, Corvallis, Oregon 97331-4003, United States.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Ishmael
authors.affiliation: Department of Pharmaceutical Sciences, Oregon State University , 203 Pharmacy Building, Corvallis, Oregon 97331-4003, United States.
authors.forename: Kerry L
authors.initials: KL
authors.lastname: McPhail
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006031:Glycosylation; D045325:HCT116 Cells; D006367:HeLa Cells; D006801:Humans; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009369:Neoplasms; D013237:Stereoisomerism; D014561:Urochordata / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D018942:Macrolides; C000589407:mandelalide A; C000609759:mandelalide E