title: ABCB1 Structural Models, Molecular Docking, and Synthesis of New Oxadiazolothiazin-3-one Inhibitors.
abstract: Docking methods are powerful tools for in silico screening and drug lead generation and optimization. Here, we describe the synthesis of new inhibitors of ABCB1 whose design was based on construction and preliminary confirmation of a model for this membrane transporter of the ATP-binding cassette family. We chose the strategy to build our three-dimensional model of the ABCB1 transporter by homology. Atomic coordinates were then assayed for their reliability using the measured activity of some oxadiazolothiazin-3-one compounds. Once established their performance by docking analysis, we synthesized new compounds whose forecasted activity was tested by MTT and cytofluorimetric assays. Our docking model of MDR1, MONBD1, seems to reliably satisfy our need to design and forecast, on the basis of their LTCC blockers ability, the inhibitory activity of new molecules on the ABCB1 transporter.
authors.affiliation: IRCCS SM-IST, U.O.S. Biopolimeri e Proteomica , Largo R. Benzi 10, 16132 Genova, Italy.
authors.forename: Camillo
authors.initials: C
authors.lastname: Rosano
authors.affiliation: IRCCS SM-IST, U.O.C. Terapia Immunologica , Largo R. Benzi 10, 16132 Genova, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Viale
authors.affiliation: Dip. di Farmacia, Università degli Studi di Napoli "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cosimelli
authors.affiliation: Dip. di Farmacia, Università degli Studi di Napoli "Federico II" , Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Elda
authors.initials: E
authors.lastname: Severi
authors.affiliation: IRCCS SM-IST, U.O.C. Terapia Immunologica , Largo R. Benzi 10, 16132 Genova, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Gangemi
authors.affiliation: Dip. di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma , Piazzale A. Moro 5, 00185 Roma, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Ciogli
authors.affiliation: IRCCS SM-IST, U.O.C. Trasferimento Genico , Largo R. Benzi 10, 16132 Genova, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: De Totero
authors.affiliation: Dip. di Chimica "G. Ciamician", Università degli Studi di Bologna , Via F. Selmi 2, 40126 Bologna, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Spinelli
keywords: ABCB1 inhibitors; LTCC blockers compounds; docking; drug design; multidrug resistance; oxadiazolothiazin-3-ones