title: Antiviral 6-amino-quinolones: molecular basis for potency and selectivity.
abstract: Structural modifications introduced in 6-amino-quinolones to increase antiviral activity can strongly affect cytotoxicity to host cells. By competition to Tat-TAR complex and binding experiments to viral and cellular DNA and RNA structures, we show that the nature of the substituent at position 7 modifies drug affinity and specificity for the nucleic acid. Interestingly, the basicity of the above substituent modulates chelation of the quinolone template to magnesium ions, which, in turn, critically affects the potency and target selectivity in the antiviral quinolone family.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, via Marzolo 5, 35131 Padova, Italy.
authors.forename: Sara N
authors.initials: SN
authors.lastname: Richter
authors.forename: Barbara
authors.initials: B
authors.lastname: Gatto
authors.forename: Oriana
authors.initials: O
authors.lastname: Tabarrini
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Fravolini
authors.forename: Manlio
authors.initials: M
authors.lastname: Palumbo
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D016923:Cell Death / Q000187:drug effects; D015696:Gene Products, tat; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D008274:Magnesium; D009696:Nucleic Acids / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000634:Aminoquinolines; D000998:Antiviral Agents; D015696:Gene Products, tat; D009696:Nucleic Acids; D008274:Magnesium