title: Synthetic α-(aminomethyl)-γ-butyrolactones and their anti-pancreatic cancer activities.
abstract: Aminated α-methylene-γ-butyrolactones, which are readily synthesized with facile control of the diastereoisomerism, provide an economical and commercially-viable alternative to the use of aminated natural products. These aminoloactones, which exhibit excellent activity against three pancreatic cancer cell lines when measured at 10 μM-Panc-1, MIA PaCa-2, and BxPC-3-and are comparable to or better than parthenolide and dimethylaminoparthenolide (DMAPT, LC-1). It has also been shown that there is an effect on the biological activity depending on the identity of the amine.
authors.affiliation: Herbert C. Brown Center for Borane Research, Department of Chemistry, Purdue University, 560 Oval Drive, West Lafayette, IN 47907-2084, USA. Electronic address: chandran@purdue.edu.
authors.forename: P Veeraraghavan
authors.initials: PV
authors.lastname: Ramachandran
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Nicponski
authors.forename: Hari N G
authors.initials: HN
authors.lastname: Nair
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Helppi
authors.forename: Pravin D
authors.initials: PD
authors.lastname: Gagare
authors.forename: C Max
authors.initials: CM
authors.lastname: Schmidt
authors.forename: Michele T
authors.initials: MT
authors.lastname: Yip-Schneider
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000586:Amination; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology; D012717:Sesquiterpenes / Q000737:chemistry / Q000633:toxicity; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; C524858:LC-1 compound; D012717:Sesquiterpenes; C002669:parthenolide; C014096:alpha-methylene gamma-butyrolactone; D015107:4-Butyrolactone
keywords: Amination; Michael addition; Pancreatic cancer; Parthenolide; α-Methylene-γ-butyrolactones