Abstract
An alarming increase in microbial resistance to traditional drugs and classical pharmacophores has spurred the search for new antimicrobial compounds. Indolone-N-oxides (INODs) possess a redox pharmacophore with promising, recently established, antimalarial activities. In this study, the anti-infectious properties of a series of INODs were investigated. The antibacterial activity was evaluated against five bacterial strains Gram-positive (Staphylococcus aureus, Enterococcus hirae), Gram-negative (Pseudomonas aeruginosa, Escherichia coli) and acid-fast (Mycobacterium tuberculosis). The antifungal activity was assessed using two fungal strains (Aspergillus niger, Candida albicans). The antileishmanial activity was tested against two leishmanial strains, axenically-cultured amastigote (Leishmania infantum, Leishmania amazonensis). The pharmacological activities are discussed as a function of structural and lipophilic characteristics. The Gram-positive bacterial strain E. hirae was found to be the most sensitive strain, whereas the Gram-negative E. coli was resistant to this family of compounds. One compound (64) was more potent than nalidixic acid against E. hirae, whereas another one (52) was equipotent as clotrimazole against C. albicans. INODs were microbe -cidal rather than -static. INODs showed good antitubercular activity in the low micromolar range (similar to ciprofloxacin). In addition, INOD-antiprotozoal potencies were confirmed against the leishmania parasite. INODs showed a broad spectrum of antimicrobial activity and offer a promising anti-infectious prototype worthy of being developed.
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Acknowledgements
This work was supported by the European Union (Redox antimalarial drug discovery, Read-Up, FP6-2004-LSH-2004-2.3.0-7, Strep n° 018602). Thanks are due to the Fondation pour la Recherche Médicale for financial support. We wish to thank E Pelissou and E Augugliaro for technical assistance.
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Ibrahim, H., Furiga, A., Najahi, E. et al. Antibacterial, antifungal and antileishmanial activities of indolone-N-oxide derivatives. J Antibiot 65, 499–504 (2012). https://doi.org/10.1038/ja.2012.60
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DOI: https://doi.org/10.1038/ja.2012.60
