title: Fluorescent probes of the isoxazole-dihydropyridine scaffold: MDR-1 binding and homology model.
abstract: Isoxazole-1,4-dihydropyridines (IDHPs) were tethered to fluorescent moieties using double activation via a lanthanide assisted Weinreb amidation. IDHP-fluorophore conjugate 3c exhibits the highest binding to date for IDHPs at the multidrug-resistance transporter (MDR-1), and IDHP-fluorophore conjugates 3c and 7 distribute selectively in SH-SY5Y cells. A homology model for IDHP binding at MDR-1 is presented which represents our current working hypothesis.
authors.affiliation: Department of Chemistry, University of Idaho, Moscow, ID 83843, United States.
authors.forename: Monika I
authors.initials: MI
authors.lastname: Szabon-Watola
authors.affiliation: NIH COBRE Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, United States.
authors.forename: Sarah V
authors.initials: SV
authors.lastname: Ulatowski
authors.affiliation: NIH COBRE Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, United States.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: George
authors.affiliation: NIH COBRE Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, United States.
authors.forename: Christina D
authors.initials: CD
authors.lastname: Hayes
authors.affiliation: NIH COBRE Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Steiger
authors.affiliation: NIH COBRE Center for Structural and Functional Neuroscience, The University of Montana, Missoula, MT 59812, United States; Department of Chemistry, University of Idaho, Moscow, ID 83843, United States. Electronic address: nicholas.natale@umontana.edu.
authors.forename: Nicholas R
authors.initials: NR
authors.lastname: Natale
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D005456:Fluorescent Dyes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008958:Models, Molecular; D015394:Molecular Structure; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D005456:Fluorescent Dyes; D007555:Isoxazoles; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D011725:Pyridines; C588331:isoxazole-1,4-dihydropyridine; C421109:multidrug resistance-associated protein 1
keywords: Dihydropyridine; Homology model; Isoxazole; Multidrug resistance transporter