Enoxacin

Henwood, Julian M.; Monk, J. Paul

doi:10.2165/00003495-198836010-00004

Cited by 46 publications

(6 citation statements)

References 115 publications

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“…To date we have focused our attention primarily on enoxacin, which is a second generation fluoroquinolone antibiotic [99]. It was used in the United States for about ten years for the treatment of urinary tract infections and gonorrhea, and was voluntarily taken from the market in the US because of adverse effects including insomnia [100].…”

Section: Introductionmentioning

confidence: 99%

Rational Identification of Enoxacin as a Novel V-ATPase-Directed Osteoclast Inhibitor

Toro¹,

Ostrov²,

Wronski³

et al. 2012

CPPS

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Binding between vacuolar H+-ATPases (V-ATPases) and microfilaments is mediated by an actin binding domain in the B-subunit. Both isoforms of mammalian B-subunit bind microfilaments with high affinity. A similar actin-binding activity has been demonstrated in the B-subunit of yeast. A conserved “profilin-like” domain in the B-subunit mediates this actin-binding activity, named due to its sequence and structural similarity to an actin-binding surface of the canonical actin binding protein profilin. Subtle mutations in the “profilin-like” domain eliminate actin binding activity without disrupting the ability of the altered protein to associate with the other subunits of V-ATPase to form a functional proton pump. Analysis of these mutated B-subunits suggests that the actin-binding activity is not required for the “housekeeping” functions of V-ATPases, but is important for certain specialized roles. In osteoclasts, the actin-binding activity is required for transport of V-ATPases to the plasma membrane, a prerequisite for bone resorption. A virtual screen led to the identification of enoxacin as a small molecule that bound to the actin-binding surface of the B2-subunit and competitively inhibited B2-subunit and actin interaction. Enoxacin disrupted osteoclastic bone resorption in vitro, but did not affect osteoblast formation or mineralization. Recently, enoxacin was identified as an inhibitor of the virulence of Candida albicans and more importantly of cancer growth and metastasis. Efforts are underway to determine the mechanisms by which enoxacin and other small molecule inhibitors of B2 and microfilament binding interaction selectively block bone resorption, the virulence of Candida, cancer growth, and metastasis.

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Section: Introductionmentioning

confidence: 99%

Rational Identification of Enoxacin as a Novel V-ATPase-Directed Osteoclast Inhibitor

Toro¹,

Ostrov²,

Wronski³

et al. 2012

CPPS

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“…Lomefloxacin exhibits antibacterial activity against a wide range of Gram-negative bacteria [15,16]. Similarly, Enoxacin also exhibits activity against Gram-negative bacteria, but shows comparatively lower efficacy against Gram-positive microorganisms [17,18]. The comprehensive examination of ADMET properties and binding energy analysis indicated that acyl transferases LpxA and LpxD exhibited a particular preference for fluoroquinolones.…”

Section: Toxicity and Adme Screeningmentioning

confidence: 99%

Unveiling Therapeutic Potential: Targeting Fusobacterium nucleatum’s Lipopolysaccharide Biosynthesis for Endodontic Infections—An In Silico Screening Study

Boreak,

Alrajab,

Nahari

et al. 2024

IJMS

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Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.

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“…Enoxacin, an antibacterial agent used for treating urinary tract infections [55], has previously been identified as a radioprotector. Using a high-throughput screening method with viability of lymphocytes as the primary readout, two classes of antibiotics (tetracyclines and fluoroquinolones) were identified as robust radioprotectors, including enoxacin [56].…”

Section: Drug Downselection Processmentioning

confidence: 99%

Radioprotective drug screening in a salivary gland tissue chip

Piraino

Chen

Mereness

et al. 2023

Preprint

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Ionizing radiation damage to the salivary glands during head and neck cancer treatment often causes a permanent loss of secretory function. Due to the resulting decrease in saliva production, patients experience difficulty with eating, speaking, and swallowing and are predisposed to oral infections and tooth decay. While the radioprotective drug amifostine is approved to prevent radiation-induced hyposalivation, it has intolerable side effects that limit its use and motivate research into discovering alternatives. To address this issue, we have developed a salivary gland mimetic (SGm) tissue chip platform for use in high-content drug discovery. Here, we report on the development and validation of in-chip assays to quantify reduced glutathione and cellular senescence (β-galactosidase) as measures of radiation damage and protection using WR-1065, the active form of amifostine. Following validation, we next tested our assays using other reported radioprotective drugs including Edaravone, Tempol, N-acetylcysteine, Rapamycin, Ex-Rad, and Palifermin. The validated assays were then used to screen a library of FDA-approved compounds for radioprotection. We screened 438 compounds, obtained 25 hits that were further tested for EC50 values and downselected using information from the PubChem database. Lead compounds were identified that are being tested in preclinical models.

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Enoxacin

Cited by 46 publications

References 115 publications

Rational Identification of Enoxacin as a Novel V-ATPase-Directed Osteoclast Inhibitor

Rational Identification of Enoxacin as a Novel V-ATPase-Directed Osteoclast Inhibitor

Unveiling Therapeutic Potential: Targeting Fusobacterium nucleatum’s Lipopolysaccharide Biosynthesis for Endodontic Infections—An In Silico Screening Study

Radioprotective drug screening in a salivary gland tissue chip

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