title: Evaluation of synthetic coumarins for antiausterity cytotoxicity against pancreatic cancers.
abstract: A series of functionalized coumarins were synthesized and evaluated for their capacity to inhibit the resistance to starvation of pancreatic cancer cells. This form of cytotoxicity, termed 'antiausterity' activity, was evaluated using a preferential cytotoxicity assay that compared cell survival in nutrient poor and nutrient rich conditions. Six of the seventeen compounds showed weak antiausterity activity against PANC-1. Compound 34 was active against PANC-1, MIA PaCa-2, and Capan-1 cancer cell lines. All of the compounds tested were simplified structural analogs of previously reported natural product leads. Six of the compounds, including 34, contain functionalized triazoles as novel potential bioisosteres of the side chain of the natural product angelmarin. Overall, the analogs were found to have low antiausterity activity relative to the corresponding natural products.
authors.affiliation: Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA.
authors.forename: Conner M
authors.initials: CM
authors.lastname: Farley
authors.affiliation: Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Dya Fita
authors.initials: DF
authors.lastname: Dibwe
authors.affiliation: Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Jun-ya
authors.initials: JY
authors.lastname: Ueda
authors.affiliation: Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hall
authors.affiliation: Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
authors.forename: Suresh
authors.initials: S
authors.lastname: Awale
authors.affiliation: Department of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA.
authors.forename: Jakob
authors.initials: J
authors.lastname: Magolan
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003374:Coumarins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013329:Structure-Activity Relationship
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001688:Biological Products; D003374:Coumarins
keywords: Antiausterity agents; Apoptosis; Coumarins; Pancreatic cancer; Starvation-resistance