Synthesis and Antimicrobial Activity of Novel 4-Hydroxy-2-quinolone Analogs.

Thitiphong Khamkhenshorngphanuch,Napasawan Plabutong,Sarisa Na Pombejra,Alongkorn Janjamratsaeng,Kanitta Manadee,Arsa Thammahong,Tanatorn Khotavivattana,Kittipat Kulkraisri

doi:10.3390/molecules25133059

Thitiphong Khamkhenshorngphanuch, Napasawan Plabutong + Show 6 more

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https://doi.org/10.3390/molecules25133059

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Abstract

Alkyl quinolone has been proven to be a privileged scaffold in the antimicrobial drug discovery pipeline. In this study, a series of new 4-hydroxy-2-quinolinone analogs containing a long alkyl side chain at C-3 and a broad range of substituents on the C-6 and C-7 positions were synthesized. The antibacterial and antifungal activities of these analogs against Staphylococcus aureus, Escherichia coli, and Aspergillus flavus were investigated. The structure-activity relationship study revealed that the length of the alkyl chain, as well as the type of substituent, has a dramatic impact on the antimicrobial activities. Particularly, the brominated analogs 3j with a nonyl side chain exhibited exceptional antifungal activities against A. flavus (half maximal inhibitory concentration (IC50) = 1.05 µg/mL), which surpassed that of the amphotericin B used as a positive control. The antibacterial activity against S. aureus, although not as potent, showed a similar trend to the antifungal activity. The data suggest that the 4-hydroxy-2-quinolone is a promising framework for the further development of new antimicrobial agents, especially for antifungal treatment.

Highlights

The infection produced by microorganisms, such as bacteria or fungi, has long been considered as one of the major global health concerns
The 4-hydroxy-2-quinolone analogs in this work were synthesized following a three-step protocol starting from isatoic anhydrides with various substituents on the aromatic ring (Figure 2)
25, 3059 protocol starting from isatoic anhydrides with various substituents on the aromatic ring (Figure 2)

Summary

Introduction

The infection produced by microorganisms, such as bacteria or fungi, has long been considered as one of the major global health concerns. In the search for a new scaffold for antimicrobial drugs, 4-hydroxy-2-quinolone, a class of heterocyclic compound, has shown great potential, as various analogs of 4-hydroxy-2-quinolone including Roquinimex (Linomide), a synthetic immunomodulator [3], have been reported to possess a Molecules 2020, 25, 3059; doi:10.3390/molecules25133059 www.mdpi.com/journal/molecules. In the search for a new scaffold for antimicrobial drugs, 4-hydroxy-2-quinolone, a class of heterocyclic compound, has shown great potential, as various analogs of 4-hydroxy-2-quinolone. Molecules 2020, 25, 3059 including Roquinimex (Linomide), a synthetic immunomodulator [3], have been reported to possess a wide range of biological activities such as antibacterial [4], antifungal [5], anticancer [6], antioxidant wide rangesoofon. Over the past few several[4], attempts have made[6], to antioxidant investigate [7], the and so on.

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