Derivatives (halogen, nitro and amino) of 8-hydroxyquinoline with highly potent antimicrobial and antioxidant activities

Abstract

8-Hydroxyquinoline (8HQ) compounds have been reported to possess diverse bioactivities. In recent years, drug repositioning has gained considerable attention in drug discovery and development. Herein, 8HQ ( 1) and its derivatives ( 2–9) bearing various substituents (amino, nitro, cyano and halogen) were investigated for their antimicrobial against 27 microorganisms (agar dilution method) and antioxidant (DPPH method) activities. The parent 8HQ ( 1) exerted a highly potent antimicrobial activity against Gram-positive bacteria including diploid fungi and yeast with MIC values in the range of 3.44–13.78 μM. Moreover, the halogenated 8HQ, especially 7-bromo-8HQ ( 4) and clioquinol ( 6), displayed a high antigrowth activity against Gram-negative bacteria compared with the parent compound ( 1). Apparently, the derivatives with a relatively high safely index, e.g., nitroxoline ( 2), exhibited strong antibacterial activity against Aeromonas hydrophila (MIC=5.26 μM) and selectively inhibited the growth of P. aeruginosa with the MIC value of 84.14 μM; cloxyquin ( 3) showed a strong activity against Listseria monocytogenes and Plesiomonas shigelloides with MIC values of 5.57 and 11.14 μM, respectively. Most compounds displayed an antioxidant activity. Specifically, 5-amino-8HQ ( 8) was shown to be the most potent antioxidant (IC ₅₀=8.70 μM) compared with the positive control ( α-tocopherol) with IC ₅₀ of 13.47 μM. The findings reveal that 8HQ derivatives are potential candidates to be further developed as antimicrobial and antioxidant agents.

Highlights

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  8-Hydroxyquinoline exerted highly potent antibacterial activity (Gram positive).

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  Nitroxoline exhibited strong antibacterial activity against Pseudomonas aeruginosa.

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  Cloxyquin displayed a high growth inhibition against Listeria monocytogenes and Plesiomonas shigelloides .

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  5-Amino-8-hydroxyquinoline exerted the most potent antioxidant activity (IC ₅₀=8.70 μM).

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  Nitroxoline and cloxyquin had a relatively high selectivity index.