title: Investigation of 5-nitrofuran derivatives: synthesis, antibacterial activity, and quantitative structure-activity relationships.
abstract: Three sets of antibacterial nitrofuran derivatives [set I, 5-R-substituted (Z)-2-(5-nitrofuran-2-ylmethylene)-3(2H)-benzofuranones (R = OCH(3), H, CH(3), C(2)H(5), nC(3)H(7), Cl, Br, CN, and NO(2)) and their 2-hydroxyphenyl and 2-acetoxyphenyl analogues; set II, 5-R-substituted (E)-1-(2-hydroxyphenyl)-3-(5-nitrofuryl)-2-propen-1-ones (R = H, CH(3), C(2)H(5), Cl, and NO(2)); and set III, 5-R-substituted (E)-1-(2-acetoxyphenyl)-3-(5-nitrofuryl)-2-propen-1-ones (R = H, CH(3); C(2)H(5), Cl, and NO(2))] were prepared and tested against a Gram-positive (Staphylococcus aureus, strain ATCC-25923) and a Gram-negative bacterium (Caulobacter crescentus, strain NA 1000). QSAR equations derived for the IC(50) values against both bacteria show negative contributions of two terms: an electronic one, expressed either by sigma, the Hammett substituent constant, or by E, the cyclic voltametric reduction potential. Another term described by an indicator variable, I(abs), is assigned the value of 0 for set I compounds and the value of 1 for sets II and III. No important contribution of the hydrophobic factor was found. For the three sets, the QSAR regressions suggest that the same structural features describe the activities for both bacteria and that, although reduction is a necessary step, it should not be the determining one. These results agree with those found for the QSAR of 5-nitroimidazole analogues.
authors.affiliation: Departamento de Química Fundamental and Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, C.P. 26077, 05513-970, São Paulo, Brazil.
authors.forename: J R
authors.initials: JR
authors.lastname: Pires
authors.forename: C
authors.initials: C
authors.lastname: Saito
authors.forename: S L
authors.initials: SL
authors.lastname: Gomes
authors.forename: A M
authors.initials: AM
authors.lastname: Giesbrecht
authors.forename: A T
authors.initials: AT
authors.lastname: Amaral
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016935:Caulobacter crescentus / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D020128:Inhibitory Concentration 50; D008826:Microbial Sensitivity Tests; D009581:Nitrofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010084:Oxidation-Reduction; D021281:Quantitative Structure-Activity Relationship; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D009581:Nitrofurans