title: Conformational analysis of two novel cytotoxic C2-substituted pyrrolo[2,3-f]quinolines in aqueous media, organic solvents, membrane bilayers and at the putative active site.
abstract: We have performed: (i) conformational analysis of two novel cytotoxic C2-substituted pyrrolo[2,3-f]quinolines 5e and 5g in deuterated dimethylsulfoxide (DMSO-d(6)) utilizing NOE results from NMR spectroscopy; (ii) molecular dynamics (MD) calculations in water, DMSO and dimyristoyl phosphatidylcholine bilayers and (iii) molecular docking and MD calculations on DNA nucleotide sequences. The obtained results for the two similar in structure molecules showed differences in: (i) their conformational properties in silico and in media that reasonably simulate the biological environment; (ii) the way they are incorporated into the lipid bilayers and therefore their diffusion ability and (iii) molecular docking capacity as it is depicted from their different binding scores.
authors.affiliation: National and Kapodistrian University of Athens, Chemistry Department, Laboratory of Organic Chemistry, Panepistimioupoli-Zografou, 15771 Athens, Greece.
authors.forename: Nicole
authors.initials: N
authors.lastname: Varvarigou
authors.forename: Grigorios
authors.initials: G
authors.lastname: Megariotis
authors.forename: Georgios
authors.initials: G
authors.lastname: Leonis
authors.forename: Eleni
authors.initials: E
authors.lastname: Vrontaki
authors.forename: Antigoni-Margarita
authors.initials: AM
authors.lastname: Maniati
authors.forename: Marilena
authors.initials: M
authors.lastname: Vlachou
authors.forename: Aphrodite
authors.initials: A
authors.lastname: Eikosipentaki
authors.forename: Rodanthi
authors.initials: R
authors.lastname: Kompogennitaki
authors.forename: Manthos G
authors.initials: MG
authors.lastname: Papadopoulos
authors.forename: Simona Golic
authors.initials: SG
authors.lastname: Grdadolnik
authors.forename: Dimitri
authors.initials: D
authors.lastname: Komiotis
authors.forename: Thomas
authors.initials: T
authors.lastname: Mavromoustakos
authors.forename: Andrew
authors.initials: A
authors.lastname: Tsotinis
mesh_terms: D020134:Catalytic Domain; D004058:Diffusion; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D011758:Pyrroles / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry*; D012996:Solutions; D012997:Solvents / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D011758:Pyrroles; D011804:Quinolines; D012996:Solutions; D012997:Solvents; C579451:pyrrolo(2,3-f)quinoline; D014867:Water; D004121:Dimethyl Sulfoxide