title: Oxoquinoline derivatives: identification and structure-activity relationship (SAR) analysis of new anti-HSV-1 agents.
abstract: Herpes simplex virus is an important human pathogen responsible for a range of diseases from mild uncomplicated mucocutaneous infections to life-threatening ones. Currently, the emergence of Herpes simplex virus resistant strains increased the need for more effective and less cytotoxic drugs for Herpes treatment. In this work, we synthesized a series of oxoquinoline derivatives and experimentally evaluated the antiviral activity against acyclovir resistant HSV-1 strain as well as their cytotoxity profile. The most active compound (3b), named here as Fluoroxaq-3b, showed a promising profile with a better cytotoxicity profile than acyclovir. The theoretical analysis of the structure-activity relationship of these compounds revealed some stereoelectronic properties such as lower LUMO energy and lipophilicity, besides a higher polar surface area and number of hydrogen bond acceptor groups as important parameters for the antiviral activity. Fluoroxaq-3b showed a good oral theoretical bioavailability, according to Lipinski rule of five, with a promising profile for further in vivo analysis.
authors.affiliation: Instituto de Biologia, LABioMol, Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Outeiro de São João Batista s/n, Centro, Niterói CEP 24020-150, RJ, Brazil.
authors.forename: Paula A
authors.initials: PA
authors.lastname: Abreu
authors.forename: Viveca A G G
authors.initials: VA
authors.lastname: da Silva
authors.forename: Fernanda C
authors.initials: FC
authors.lastname: Santos
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Cecília S
authors.initials: CS
authors.lastname: Riscado
authors.forename: Mariana T
authors.initials: MT
authors.lastname: de Souza
authors.forename: Camilly P
authors.initials: CP
authors.lastname: Ribeiro
authors.forename: Juliana E
authors.initials: JE
authors.lastname: Barbosa
authors.forename: Cláudio C C
authors.initials: CC
authors.lastname: dos Santos
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Viviane
authors.initials: V
authors.lastname: Lione
authors.forename: Bianca A M
authors.initials: BA
authors.lastname: Correa
authors.forename: Anna C
authors.initials: AC
authors.lastname: Cunha
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Maria C B V
authors.initials: MC
authors.lastname: de Souza
authors.forename: Izabel C N P
authors.initials: IC
authors.lastname: Paixão
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D006561:Herpes Simplex / Q000188:drug therapy / Q000821:virology*; D018259:Herpesvirus 1, Human / Q000187:drug effects*; D006801:Humans; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D015363:Quinolones