Phenanthrolinic analogs of quinolones show antibacterial activity against M. tuberculosis

Songuigama, Coulibaly; Cimino, Mena; Ouattara, Mahama; Lecoutey, Cédric; Buchieri, Maria V.; Alonso-Rodriguez, Noelia; Briffotaux, Julien; Mornico, Damien; Gicquel, Brigitte; Rochais, Christophe; Dallemagne, Patrick

doi:10.1016/j.ejmech.2020.112821

Cited by 10 publications

(10 citation statements)

References 23 publications

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“…Therefore, one possibility is to preselect compounds based on other parameters, without necessarily increasing the likelihood of identifying a PTC. For instance, our candidate PTC included primarily small molecule compounds with no apparent activity 22 , and a few quinolone analogs 23 , which were the source of our hits. However, for a deeper characterization, we focused on the PTC that had not only the strongest effect on the SOS indices but was also the most soluble.…”

Section: Discussionmentioning

confidence: 99%

“…We tested two categories of compounds: 65 fragment compounds with millimolar activity 22 ; and 7 phenanthroline derivatives with micromolar activity 23 (Supplementary Table 1). The experimental setup was divided into three stages: 6 hours of pre-growth in standard medium (PRE); 6 hours of exposure to subinhibitory concentrations of candidate PTC or control molecules (DUR); and 6 hours of washing (POST) (Fig.…”

Section: Dynamic Single-cell Screening For Pheno-tuning Compounds (µD...mentioning

confidence: 99%

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Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Mistretta

Cimino

Campagne

et al. 2023

Preprint

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Drug-recalcitrant infections are a leading global-health concern. Bacterial cells benefit from phenotypic variation, which can suggest effective anti-microbial strategies. However, probing phenotypic variation entails spatiotemporal analysis of individual cells that is technically challenging, and hard to integrate into drug discovery. To address this, we developed a flow-controlled multi-condition microfluidic platform suitable for imaging two-dimensional growth of bacterial cells, compressed inside separate microchambers by a soft hydro-pneumatic membrane. With this platform, we implemented a dynamic single-cell screening for compounds that induce a phenotypic change while decreasing cell-to-cell variation, aiming to undermine the bacterial population, making it more vulnerable to other drugs. We first applied this strategy to mycobacteria, as tuberculosis poses a major public-health threat. Our top hit impairsMycobacterium tuberculosisvia a peculiar mode of action and enhances other anti-tubercular drugs. This work proves that pheno-tuning compounds represent a successful approach to tackle pathogens that are increasingly difficult to treat.

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Section: Discussionmentioning

confidence: 99%

Section: Dynamic Single-cell Screening For Pheno-tuning Compounds (µD...mentioning

confidence: 99%

Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Mistretta

Cimino

Campagne

et al. 2023

Preprint

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“…Tuberculosis (TB) remains one of the world's most lethal infectious illnesses, killing an estimated 1.5 million people each year [1]. In 2018, the WHO reported a range of estimated incident cases between 9.0 and 11.1 million patients in addition to notifying 7.0 million new cases of TB [2].…”

Section: Introductionmentioning

confidence: 99%

“…New hopes were provided through the approval of bedaquiline by the FDA. Rapidly, the failure of the clinically introduced drug by its first resistant M. tuberculosis isolate dramatically terminated the story [1]. As a result, the creation of novel anti-TB medications is urgently required.…”

Section: Introductionmentioning

confidence: 99%

Development of Novel Isatin-Tethered Quinolines as Anti-Tubercular Agents against Multi and Extensively Drug-Resistant Mycobacterium tuberculosis

et al. 2022

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We describe the design and synthesis of two isatin-tethered quinolines series (Q6a–h and Q8a–h), in connection with our research interest in developing novel isatin-bearing anti-tubercular candidates. In a previous study, a series of small molecules bearing a quinoline-3-carbohydrazone moiety was developed as anti-tubercular agents, and compound IV disclosed the highest potency with MIC value equal to 6.24 µg/mL. In the current work, we adopted the bioisosteric replacement approach to replace the 3,4,5-trimethoxy-benzylidene moiety in the lead compound IV with the isatin motif, a privileged scaffold in the TB drug discovery, to furnish the first series of target molecules Q6a–h. Thereafter, the isatin motif was N-substituted with either a methyl or benzyl group to furnish the second series Q8a–h. All of the designed quinoilne-isatin conjugates Q6a–h and Q8a–h were synthesized and then biologically assessed for anti-tubercular actions towards drug-susceptible, MDR, and XDR strains. Superiorly, the N-benzyl-bearing compound Q8b possessed the best activities against the examined M. tuberculosis strains with MICs equal 0.06, 0.24, and 1.95 µg/mL, respectively.

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“…At present, the commercial antibacterial modification of emulsion (SA) are mainly based on releasable antibacterial agents, such as metals/metallic oxide, 13,14 aminoglycosides, 15 quinolones, 16 chlorhexidine, 17 triclosan, 18 and so forth. However, the release of antibacterial agents has several disadvantages, such as the pollution of environment, 19,20 stimulation to the human body, 21 short antibacterial durability 22 and even induce antibiotic resistance of bacterias 23 .…”

Section: Introductionmentioning

confidence: 99%

Preparation and properties of antibacterial styrene‐acrylic emulsion based on bis‐quaternary ammonium salt‐containing mono‐methacrylates as polymerizable antibacterial agents

Zhou

Xiong³

et al. 2021

Polymers for Advanced Techs

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With the aim to prepare antibacterial styrene‐acrylic emulsion, a series of bis‐quaternary ammonium salt‐containing mono‐methacrylates MEQABr‐x(x = 12, 14, 16) were synthesized as polymerizable antibacterial agents via two steps. The chemical structures of MEQABr‐x(x = 12, 14, 16) were confirmed by proton nuclear magnetic resonance (1H‐NMR) and Fourier transform infrared (FTIR). The Minimum inhibitory concentration (MIC), Minimum bactericidal concentration (MBC), and Critical micelle moncentration (CMC) results showed that MEQABr‐x(x = 12, 14, 16) had antibacterial properties and surface properties which was influenced by its alkyl chain length. The antibacterial emulsion (SAQx‐n) was synthesized by emulsion polymerization of styrene (St), butyl acrylate (BA), acrylic acid (AA) and MEQABr‐x(x = 12, 14, 16). The structures of its films (SAQx‐n‐F) were characterized by attenuated total reflectance‐FTIR. The effects of MEQABr‐14 content or alkyl chain length of MEQABr‐x(x = 12, 14, 16) on emulsion and its films were investigated in the aspect of particle sizes, pencil hardness, adhesive force grade, thermal stabilities, surface morphology, particle morphology, and so forth. The films (SAQx‐9‐F) with 9 wt% content of MEQABr‐x(x = 12, 14, 16) showed the nearly 100% antibacterial rate against Escherichia coli and Staphylococcus aureus, indicating its potential to be used as antibacterial coating.

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Phenanthrolinic analogs of quinolones show antibacterial activity against M. tuberculosis

Cited by 10 publications

References 23 publications

Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Dynamic microfluidic single-cell screening identifies pheno-tuning compounds to potentiate tuberculosis therapy

Development of Novel Isatin-Tethered Quinolines as Anti-Tubercular Agents against Multi and Extensively Drug-Resistant Mycobacterium tuberculosis

Preparation and properties of antibacterial styrene‐acrylic emulsion based on bis‐quaternary ammonium salt‐containing mono‐methacrylates as polymerizable antibacterial agents

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