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Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study

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Abstract

The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16 µg/mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2 µg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal.

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Acknowledgments

The work described was supported by the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (Project P10-AGR5822).

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Authors and Affiliations

  1. Área de Gestión Sanitaria Norte de Cádiz, Hospital de Jerez, Unidad de Gestión Clínica de Enfermedades Infecciosas y Microbiología, Ronda de circunvalación s/n, 11407, Jerez, Cádiz, Spain

    Juan M. Sánchez-Calvo

  2. Grupo de Alelopatía, Departamento de Química Orgánica, Instituto de Biomoléculas (INBIO), Facultad de Ciencias, Universidad de Cádiz, Campus de Excelencia Internacional Agroalimentario (ceiA3), C/República Saharaui, n 7, 11510, Puerto Real, Cádiz, Spain

    Gara R. Barbero, Guillermo Guerrero-Vásquez, Alexandra G. Durán, José M. G. Molinillo & Francisco A. Macías

  3. Departamento de Anatomía Patológica, Biología Celular, Histología, Historia de la Ciencia, Medicina Legal y Forense y Toxicología, Facultad de Medicina, Plaza Fragela, 9, 11003, Cádiz, Spain

    Mariola Macías

  4. Unidad de Gestión Clínica de Microbiología, Instituto de Biomoléculas (INBIO), Hospital Universitario Puerta del Mar, Avenida Ana de Viya, 21, 11009, Cádiz, Spain

    Manuel A. Rodríguez-Iglesias

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  1. Juan M. Sánchez-Calvo
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  2. Gara R. Barbero
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  3. Guillermo Guerrero-Vásquez
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  4. Alexandra G. Durán
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  5. Mariola Macías
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  6. Manuel A. Rodríguez-Iglesias
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Correspondence to Manuel A. Rodríguez-Iglesias or José M. G. Molinillo.

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Sánchez-Calvo, J.M., Barbero, G.R., Guerrero-Vásquez, G. et al. Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study. Med Chem Res 25, 1274–1285 (2016). https://doi.org/10.1007/s00044-016-1550-x

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