title: Development of6H-Chromeno[3,4-c]pyrido[3',2':4,5]thieno[2,3-e]pyridazin-6-ones as Par-4 Secretagogues.
abstract: Nitrosation and cyclization of 4-(3-aminothieno[2,3-b]pyridine-2-yl)-2H-chromen-2-ones1afforded substituted6H-chromeno[3,4-c]pyrido[3',2':4,5]thieno[2,3-e]pyridazin-6-ones2that inhibited the intermediary filament protein, vimentin, at low micromolar concentrations. This inhibition promoted the secretion of Prostate Apoptosis Response-4 protein (Par-4), which selectively triggered apoptosis in prostate cancer cells such as CWR22Rv1, LNCaP-derivative C4-2B, PC-3 and its aggressive analog, PC-3 MM2.
authors.affiliation: Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Science of Ukraine, Kyiv 02094, Ukraine.
authors.forename: Mykhaylo S
authors.initials: MS
authors.lastname: Frasinyuk
authors.affiliation: Taras Shevchenko Kyiv National University, Kyiv 01033, Ukraine.
authors.forename: Svitlana P
authors.initials: SP
authors.lastname: Bondarenko
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, United States ; Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, United States.
authors.forename: Vitaliy M
authors.initials: VM
authors.lastname: Sviripa
authors.affiliation: Department of Radiation Medicine, College of Medicine; University of Kentucky, Lexington, KY 40536-0096, United States.
authors.forename: Ravshan
authors.initials: R
authors.lastname: Burikhanov
authors.affiliation: Department of Radiation Medicine, College of Medicine; University of Kentucky, Lexington, KY 40536-0096, United States ; Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, United States.
authors.forename: Vivek M
authors.initials: VM
authors.lastname: Rangnekar
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, United States ; Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, United States.
authors.forename: Chunming
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, United States ; Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, United States ; Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, KY 40536-0093, United States.
authors.forename: David S
authors.initials: DS
authors.lastname: Watt
keywords: Par-4; Prostate Apoptosis Response-4 protein; coumarin; prostate cancer; pyridazine; vimentin