title: Identification of nor-β-lapachone derivatives as potential antibacterial compounds against Enterococcus faecalis clinical strain.
abstract: A broad-spectrum antibiotic therapy has led to medical complications and emergence of multiresistant bacteria including Enterococcus faecalis. In this study, we designed, synthesized, and evaluated the antibacterial activity of 13 nor-β-lapachone derivatives against a drug resistant E. faecalis strain. Two triazole substituted compounds (1e = 8 μg/ml and 1c = 16 μg/ml) and the non-substituted derivative (1a = 8 μg/ml) were promising compared to chloramphenicol (12 μg/ml), an antibiotic currently available in the market. We also performed a structure-activity relationship analysis using a molecular modeling approach that pointed the low HOMO energy values; HOMO density concentrated on the nor-β-lapachone ring, lipophilicity, solubility and number HBA as important stereoelectronic features for the antibacterial profile. In addition the triazole compounds presented low theoretical toxicity profile, and drug-score higher than commercial antibiotics also fulfilling the Lipinski "Rule of Five", which pointed them as promising candidates for further studies in infections caused by multiresistant E. faecalis hospital strains.
authors.affiliation: Instituto de Biologia, Departamento de Biologia Celular e Molecular, Universidade Federal Fluminense, Outeiro São João Batista s/n-Campus Valonguinho, Niterói, RJ, CEP 24020-150, Brazil.
authors.forename: André L
authors.initials: AL
authors.lastname: Lourenço
authors.forename: Paula A
authors.initials: PA
authors.lastname: Abreu
authors.forename: Bruno
authors.initials: B
authors.lastname: Leal
authors.forename: Eufrânio N
authors.initials: EN
authors.lastname: da Silva Júnior
authors.forename: Antonio V
authors.initials: AV
authors.lastname: Pinto
authors.forename: Maria do Carmo F R
authors.initials: Mdo C
authors.lastname: Pinto
authors.forename: Alessandra M T
authors.initials: AM
authors.lastname: Souza
authors.forename: Juliana S
authors.initials: JS
authors.lastname: Novais
authors.forename: Marcela B
authors.initials: MB
authors.lastname: Paiva
authors.forename: Lucio M
authors.initials: LM
authors.lastname: Cabral
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Rodrigues
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013293:Enterococcus faecalis / Q000187:drug effects* / Q000302:isolation & purification; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; C014638:beta-lapachone