title: Studies of Staphylococcus aureus FabI inhibitors: fragment-based approach based on holographic structure-activity relationship analyses.
abstract: OBJECTIVE
  FabI is a key enzyme in the fatty acid metabolism of Gram-positive bacteria such as Staphylococcus aureus and is an established drug target for known antibiotics such as triclosan. However, due to increasing antibacterial resistance, there is an urgent demand for new drug discovery. Recently, aminopyridine derivatives have been proposed as promising competitive inhibitors of FabI.
  
  
  METHODS
  In the present study, holographic structure-activity relationship (HQSAR) analyses were employed for determining structural contributions of a series containing 105 FabI inhibitors.
  
  
  CONCLUSIONS
  The final HQSAR model was robust and predictive according to statistical validation (q2and r2predequal to 0.696 and 0.854, respectively) and could be further employed to generate fragment contribution maps. Then, final HQSAR model together with FabI active site information can be useful for designing novel bioactive ligands.
authors.affiliation: Unit for Drug Discovery, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, SP 05508-000, Brazil.
authors.forename: Thales
authors.initials: T
authors.lastname: Kronenberger
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Leonardo Rander
authors.initials: LR
authors.lastname: Asse
authors.affiliation: Unit for Drug Discovery, Departamento de Parasitologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, SP 05508-000, Brazil.
authors.forename: Carsten
authors.initials: C
authors.lastname: Wrenger
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade de São Paulo, Av. Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil.
authors.forename: Gustavo Henrique Goulart
authors.initials: GH
authors.lastname: Trossini
authors.affiliation: Escola de Artes, Ciências e Humanidades, Universidade de São Paulo, Av. Arlindo Bettio, 1000, São Paulo, SP 03828-000, Brazil.|Centro de Ciências Naturais e Humanas, Universidade Federal do ABC, Av. dos Estados, 5001, Santo André, SP 09210-580, Brazil.
authors.forename: Kathia Maria
authors.initials: KM
authors.lastname: Honorio
authors.affiliation: Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627 - Pampulha, Belo Horizonte, MG 31270-901, Brazil.
authors.forename: Vinicius Gonçalves
authors.initials: VG
authors.lastname: Maltarollo
keywords: FabI; HQSAR; methicillin-resistant Staphylococcus aureus