Discovery of novel halogenated 8‐hydroxyquinoline‐based anti‐MRSA agents: In vitro and QSAR studies

Abstract

Methicillin‐resistant Staphylococcus aureus (MRSA) infection has been considered to be one of global health problems due to limited classes of effective antimicrobial drugs. Herein, 8‐hydroxyquinoline (8HQ) and its derivatives (1‐7) were investigated for their anti‐MRSA and antioxidant activities. Cloxyquin (2), a halogenated 8HQ, exerted the highest antimicrobial activity (MIC50 ≤ 5.57 μM) with high safety index, whereas an amino‐derivative 7 showed the strongest antioxidant activity. Additionally, quantitative structure‐activity relationship (QSAR) study demonstrated that mass, polarizability, topological charge, and van der Waals volume are essential properties governing the anti‐MRSA activity. Taken together, cloxyquin was highlighted as a promising compound for further development as a novel anti‐MRSA agent. QSAR findings would also benefit for further rational design of novel 8HQ‐based compounds to combat the MRSA resistance.

Insight into the Molecular Interaction of Cloxyquin (5-chloro-8-hydroxyquinoline) with Bovine Serum Albumin: Biophysical Analysis and Computational Simulation

“…This observation may suggest the formation of ground-state complex between BSA and cloxyquin [22]. (1), warfarin (2), ibuprofen (3), and digitoxin (4).…”

“…f a is the fraction of accessible fluorescence. F 0 , F, and [Q] serve as the same denotations as the aforementioned in Equation (1). The F 0 /(F 0 − F) versus 1/[Q] plots generated the slight concave downward curves, suggested to be the biphasic binding behavior between cloxyquin and BSA ( Figure 4).…”

“…BSA (4 µM) was titrated with various concentrations of cloxyquin (0, 1,5,10,15,20,25,30,40,60,70, and 80 µM) at different temperatures including 290, 300, and 310 K. The reactions were carried out in duplicate and its fluorescence spectra were detected in a range of 285-450 nm upon the excitation wavelength of 280 nm by using a QuantaMaster™ 40 spectrofluorometer (Photon Technology International, Inc., London, ON, Canada). The bandwidths of both excitation and emission units were set to be 1 nm.…”

“…Cloxyquin (5-chloro-8-hydroxyquinoline; Figure 1 is a chlorinated derivative of 8-hydroxyquinoline possessing diverse bioactivities and therapeutic potentials. Cloxyquin has been reported to exhibit high bactericidal effect against methicillin-resistant Staphylococcus aureus isolated from clinical isolates [1]. It exerts strong antibacterial activities toward Listeria monocytogenes (minimum inhibition concentration; MIC = 5.57 µM) and Plesiomonas shigelloides (MIC = 11.14 µM) [2].…”

In vitro antimicrobial combinatory effect of Cinnamomum cassia essential oil with 8‐hydroxyquinoline against Staphylococcus aureus in liquid and vapour phase

“…The possible future antimicrobial combinatory testing of CCEO together with 8-HQ derivatives (e.g. 5-chloro-7-iodo-8HQ, 5-chloro-8HQ), which have previously been reported to exhibit a significant antimicrobial activity against different strains of S. aureus (Cherdtrakulkiat et al 2016;Cherdtrakulkiat et al 2019), could also bring a better understanding of interactions between these agents.…”