Identification of Nor-β-Lapachone Derivatives as Potential Antibacterial Compounds against Enterococcus faecalis Clinical Strain
2011
Lourenço, André L. | Abreu, Paula A. | Leal, Bruno | da Silva Júnior, Eufrânio N. | Pinto, Antonio V. | Pinto, Maria do Carmo F. R. | Souza, Alessandra M. T. | Novais, Juliana S. | Paiva, Marcela B. | Cabral, Lucio M. | Rodrigues, Carlos R. | Ferreira, Vitor F. | Castro, Helena C.
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.
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