title: Exploring 5-nitrofuran derivatives against nosocomial pathogens: synthesis, antimicrobial activity and chemometric analysis.
abstract: The burden of nosocomial or health care-associated infection (HCAI) is increasing worldwide. According to the World Health Organization (WHO), it is several fold higher in low- and middle-income countries. Considering the multidrug-resistant infections, the development of new and more effective drugs is crucial. Herein, two series (I and II) of 5-nitrofuran derivatives were designed, synthesized and assayed against microorganisms, including Gram-positive and -negative bacteria, and fungi. The pathogens screened was directly related to either the most currently relevant HCAI, or to multidrug-resistant infection caused by MRSA/VRSA strains, for instance. The sets I and II were composed by substituted-[N'-(5-nitrofuran-2-yl)methylene]benzhydrazide and 3-acetyl-5-(substituted-phenyl)-2-(5-nitro-furan-2-yl)-2,3-dihydro-1,3,4-oxadiazole compounds, respectively. The selection of the substituent groups was based upon physicochemical properties, such as hydrophobicity and electronic effect. The compounds have showed better activity against Staphylococcus aureus, Escherichia coli, and Enterococcus faecalis. The findings from S. aureus strain, which was more susceptible, were used to investigate the intersamples and intervariables relationships by applying chemometric methods. It is noteworthy that the compound 4-butyl-[N'-(5-nitrofuran-2-yl)methylene]benzhydrazide has showed similar MIC value to vancomycin, which is the reference drug for multidrug-resistant S. aureus infections. Taken the findings together, the 5-nitrofuran derivatives might be indeed considered as promising hits to develop novel antimicrobial drugs to fight against nosocomial infection.
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmacy, University of São Paulo, Av. Prof Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil. Electronic address: rodrigo.zorzi@gmail.com.
authors.forename: Rodrigo Rocha
authors.initials: RR
authors.lastname: Zorzi
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmacy, University of São Paulo, Av. Prof Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil. Electronic address: sdjorge@gmail.com.
authors.forename: Salomão Dória
authors.initials: SD
authors.lastname: Jorge
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmacy, University of São Paulo, Av. Prof Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil.
authors.forename: Fanny
authors.initials: F
authors.lastname: Palace-Berl
authors.affiliation: Laboratory of Biochemistry and Biophysics, Butantan Institute, São Paulo, SP 05503-900, Brazil.
authors.forename: Kerly Fernanda Mesquita
authors.initials: KF
authors.lastname: Pasqualoto
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmacy, University of São Paulo, Av. Prof Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil.
authors.forename: Leandro de Sá
authors.initials: Lde S
authors.lastname: Bortolozzo
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmacy, University of São Paulo, Av. Prof Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil.
authors.forename: André Murillo
authors.initials: AM
authors.lastname: de Castro Siqueira
authors.affiliation: Department of Biochemical and Pharmaceutical Technology, Faculty of Pharmacy, University of São Paulo, Av. Prof Lineu Prestes, 580, São Paulo, SP 05508-900, Brazil.
authors.forename: Leoberto Costa
authors.initials: LC
authors.lastname: Tavares
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology*; D004305:Dose-Response Relationship, Drug; D005658:Fungi / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009581:Nitrofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D025341:Principal Component Analysis; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D009581:Nitrofurans
keywords: 5-Nitrofuran derivatives; Bacterial resistance; Exploratory data analysis; Molecular modification; Nosocomial infection