title: Synthesis and evaluation of macrocyclic diarylether heptanoid natural products and their analogs.
abstract: The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-κB. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growth inhibition and apoptosis.
authors.affiliation: Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Vashti C
authors.initials: VC
authors.lastname: Bryant
authors.forename: G D
authors.initials: GD
authors.lastname: Kishore Kumar
authors.forename: Abijah M
authors.initials: AM
authors.lastname: Nyong
authors.forename: Amarnath
authors.initials: A
authors.lastname: Natarajan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004986:Ether / Q000031:analogs & derivatives*; D057809:HEK293 Cells; D006801:Humans; D008956:Models, Chemical; D016328:NF-kappa B / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001688:Biological Products; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D004986:Ether