Search Results (16)

Background: Despite tremendous advances in antiretroviral therapy (ART) against HIV-1 infections, no cure or vaccination is available. Therefore, discovering novel therapeutic strategies remains an urgent need. In that sense, miRNAs and miRNA therapeutics have moved intensively into the focus of recent HIV-1-related investigations. A strong reciprocal interdependence has been demonstrated between HIV-1 infection and changes of the intrinsic cellular miRNA milieu. This interrelationship may direct potential alterations of the host cells’ environment beneficial for the virus or its suppression of replication. Whether this tightly balanced and controlled battle can be exploited therapeutically remains to be further addressed. In this context, the fluoroquinolone antibiotic Enoxacin has been demonstrated as a potent modulator of miRNA processing. Here, we test the hypothesis that this applies also to selected HIV-1-related miRNAs. Methods: We studied the effect of Enoxacin on HIV-1 replication coupled with miRNA qRT-PCR analysis of HIV-1-related miRNAs in CEM-SS and MT-4 T-cells. The effects of miRNA mimic transfections combined with Enoxacin treatment on HIV-1 replication were assessed. Finally, we employed an in vitro DICER1 cleavage assay to study the effects of Enoxacin on a pro-HIV-1 miRNA hsa-miR-132 processing. Results: We established that Enoxacin, but not the structurally similar compound nalidixic acid, exhibits strong anti-HIV-1 effects in the T-cell line CEM-SS, but not MT-4. We provide experimental data that this effect of Enoxacin is partly attributed to the specific downregulation of mature hsa-miR-132-3p, but not other tested pro- or anti-HIV-1 miRNAs, which is likely due to affecting DICER1 processing. Conclusions: Our findings show an anti-retroviral activity of Enoxacin at least in part by downregulation of hsa-miR-132-3p, which may be relevant for future antiviral therapeutic applications by modulation of the RNA interference pathway. Full article

A comprehensive review of advances in the synthesis and biological applications of enoxacin (1, referred to as ENX)-based compounds is presented. ENX, a second-generation fluoroquinolone (FQ), is a prominent 1,8-naphthyridine containing compounds studied in medicinal chemistry. Quinolones, a class of synthetic antibiotics, are crucial building blocks for designing multi-biological libraries due to their inhibitory properties against DNA replication. Chemical modifications at positions 3 and 7 of the quinolone structure can transform antibacterial FQs into anticancer analogs. ENX and its derivatives have been examined for various therapeutic applications, including anticancer, antiviral, and potential treatment against COVID-19. Several synthetic methodologies have been devised for the efficient and versatile synthesis of ENX and its derivatives. This review emphasizes all-inclusive developments in the synthesis of ENX derivatives, focusing on modifications at C3 (carboxylic acid, Part A), C7 (piperazinyl, Part B), and other modifications (Parts A and B). The reactions considered were chosen based on their reproducibility, ease of execution, accessibility, and the availability of the methodology reported in the literature. This review provides valuable insights into the medicinal properties of these compounds, highlighting their potential as therapeutic agents in various fields. Full article

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. Full article

An accurate and simple screening method has been developed for the determination of fluoroquinolone antibiotics. Carbon dots were synthesized by simple hydrothermal treatment as highly fluorescent nano-sensors. They were subsequently used in the synthesis of organic-based molecularly imprinted polymers to develop fluorescence-based polymeric composites using enoxacin as a representative dummy template molecule of fluoroquinolones. The method was optimized concerning the pH of the medium and composite concentration. The normalized fluorescence intensity showed efficient quenching under optimized conditions upon successive addition of the template, with an excellent correlation coefficient. The proposed method was applied to eight other fluoroquinolones, exhibiting, in all cases, good correlation coefficients (0.65–0.992) within the same linearity range (0.03–2.60 mg mL⁻¹). Excellent detection and quantification limits were been obtained for the target analytes down to 0.062 and 0.186 mg L⁻¹, respectively. All studied analytes showed no interference with enrofloxacin, the most commonly used veterinary fluoroquinolone, with a percentage of cross-reactivity varying from 89.00 to 540.00%. This method was applied successfully for the determination of enrofloxacin in three different types of meat samples: beef, pork, and chicken, with good recoveries varying from 70 to 100% at three levels. This new procedure is an easy analytical method that can be useful as a screening method for monitoring the environmental hazard of fluoroquinolones in quality control laboratories. Full article

Residual quinolones in food that exceed their maximum residue limit (MRL) are harmful to human health. However, the existing methods used for testing these residues have limitations; so, we developed a new limit test method called TLC-SERS to rapidly determine the levels of residues of the following: enrofloxacin (A), ciprofloxacin (B), ofloxacin (C), fleroxacin (D), sparfloxacin (E), enoxacin (F), gatifloxacin (G), and nadifloxacin (H). The residues ware preliminarily separated via TLC. The tested compounds’ position on a thin-layer plate were labeled using their relative R_f under 254 nm ultraviolet light, and an appropriate amount of nanometer silver solution was added to the position. The silver on the plate was irradiated with a 532 nm laser to obtain the SERSs of the compounds. The results show significant differences in the SERS of the eight quinolones: the LODs of H, A, D, E, C, G, F, and B were 9.0, 12.6, 8.9, 19.0, 8.0, 8.7, 19.0, and 12.6 ng/mL, respectively; and the RSD was ≤4.9% for the SERS of each quinolone. The limit test results of 20 samples are consistent with those obtained via UPLC–MS/MS. The results indicate that TLC-SERS is a specific, sensitive, stable, and accurate method, providing a new reference for the rapid limit test of harmful residues in foods. Full article

Fluoroquinolone (FQ) is a type of widely used antibiotic in agriculture and aquaculture, and exposure to low doses of FQs may result in the transfer of resistance between animal and human pathogens. Based on the optimization of the operating parameters, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) standard curve was constructed for the simultaneous detection of 13 FQs, including enrofloxacin (ENR), ciprofloxacin (CIP), sarafloxacin (SAR), ofloxacin (OFL), norfloxacin (NOR), pefloxacin mesylate (PM), pefloxacin (PEF), enoxacin (ENX), marbofloxacin (MAR), fleroxacin (FLE), lomefloxacin (LOM), danofloxacin (DAN), and difloxacin (DIF). The limit of detection (LOD, computed as IC₁₀) and sensitivity (IC₅₀) of the ic-ELISA for ENR were 0.59 μg/L and 19.23 μg/L, respectively. The precision and dependability of the detection results of this ic-ELISA were properly verified by HPLC in Rana catesbeianus samples. This indicated that the established ic-ELISA approach could be utilized to determine the FQs in Rana catesbeianus. In addition, this ic-ELISA, based on a broad-spectrum antibody, provides a technical reference and potential strategy for an immunoassay of hazard factors with similar structure. Full article

Virus-encoded microRNAs were first reported in the Epstein–Barr virus in 2004. Subsequently, a few hundred viral miRNAs have been identified, mainly in DNA viruses belonging to the herpesviridae family. To date, only 30 viral miRNAs encoded by RNA viruses are reported by miRBase. Since the outbreak of the SARS-CoV-2 pandemic, several studies have predicted and, in some cases, experimentally validated miRNAs originating from the positive strand of the SARS-CoV-2 genome. By integrating NGS data analysis and qRT-PCR approaches, we found that SARS-CoV-2 also encodes for a viral miRNA arising from the minus (antisense) strand of the viral genome, in the region encoding for ORF1ab, herein referred to as SARS-CoV-2-miR-AS1. Our data show that the expression of this microRNA increases in a time course analysis of SARS-CoV-2 infected cells. Furthermore, enoxacin treatment enhances the accumulation of the mature SARS-CoV-2-miR-AS1 in SARS-CoV-2 infected cells, arguing for a Dicer-dependent processing of this small RNA. In silico analysis suggests that SARS-CoV-2-miR-AS1 targets a set of genes which are translationally repressed during SARS-CoV-2 infection. We experimentally validated that SARS-CoV-2-miR-AS1 targets FOS, thus repressing the AP-1 transcription factor activity in human cells. Full article

The removal of enoxacin (ENO), a broad-spectrum fluoroquinolone antibiotic, was firstly examined in a sulfate-reducing up-flow sludge bed (SRUSB) bioreactor over a long-term operation (366 days). Over 94% of the ENO was removed in the SRUSB bioreactor via adsorption and biodegradation at different initial ENO concentrations (i.e., 25–1000 μg/L). Based on the results of the batch tests, the sulfate-reducing sludge exhibited a high ENO adsorption capacity within a k_d of 22.7–28.9 L/g-SS. The adsorption of ENO by the sulfate-reducing sludge was a spontaneous (ΔG° < 0 KJ/mol) and exothermic (ΔH° < 0 KJ/mol) process including physisorption and chemisorption (absolute value of ΔH° = 51.882 KJ/mol). Moreover, ENO was effectively biodegraded by the sulfate-reducing sludge within specific rates of 2.5–161.3 μg/g-SS/d. The ENO biodegradation process in the sulfate-reducing sludge system was most accurately described by the first-order kinetic model. Collectively, our findings provide insight into the applicability of a sulfate-reducing sludge system for ENO-contaminated wastewater treatment. Full article

Enoxacin as a second-generation synthetic quinolone is known for its antibacterial action; however, in recent years there have been studies focusing on its anticancer potential. Interestingly, it turns out that compared to other fluoroquinolones, enoxacin exhibits uncommon cytotoxic properties. Besides its influence on apoptosis, the cell cycle and cell growth, it exhibits a regulatory action on microRNA biogenesis. It was revealed that the molecular targets of the enoxacin-mediated inhibition of osteoclastogenesis are vacuolar H⁺-ATPase subunits and the c-Jun N-terminal kinase signaling pathway, causing a decrease in cell invasiveness. Interestingly, the prooxidative nature of the subjected fluoroquinolone enhanced the cytotoxic effect. Crucial for the anticancer activity were the carboxyl group at the third carbon atom, fluorine at the seventh carbon atom and nitrogen at the eighth position of naphyridine. Modifications of the parent drug improved the induction of oxidative stress, cell cycle arrest and the dysregulation of microRNA. The inhibition of V-ATPase–microfilament binding was also observed. Enoxacin strongly affected various cancer but not normal cells, excluding keratinocytes, which suffered from phototoxicity. It seems to be an underestimated anticancer drug with pleiotropic action. Furthermore, its usage as a safe antibiotic with well-known pharmacokinetics and selectivity will enhance the development of anticancer treatment strategies. This review covers articles published within the years 2000–2021, with a strong focus on the recent years (2016–2021). However, some canonical papers published in twentieth century are also mentioned. Full article

The binding of fluoroquinolones, the most commonly prescribed antibiotics, with melanin is well explored. However, their binding patterns and exact mechanism of interaction with tyrosinase, a key enzyme in melanogenesis, are not explored yet. Thus, in the present study, seven fluoroquinolone drugs were selected to characterize their interactions with the tyrosinase enzyme: ciprofloxacin, enoxacin sesquihydrate, ofloxacin, levofloxacin, sparfloxacin, moxifloxacin and gemifloxacin. The results confirmed that all the drugs execute excellent enzyme activity, with an inhibition range from IC₅₀ = 28 ± 4 to 50 ± 1.9 μM, outperforming the standard hydroquinone (IC₅₀ = 170 μM). Later, kinetic studies revealed that all the drugs showed irreversible, but mixed-type, tyrosinase inhibition, with a preferentially competitive mode of action. Further, 2D and 3D docked complexes and binding analyses confirmed their significant interactions in the active region of the target enzyme, sufficient for the downstream signaling responsible for the observed tyrosinase inhibition. Thus, this is the first report demonstrating their mechanism of tyrosinase inhibition, critical for melanin-dependent responses, including toxicity. Full article

Repurposing FDA-approved drugs that treat respiratory infections caused by coronaviruses, such as SARS-CoV-2 and MERS-CoV, could quickly provide much needed antiviral therapies. In the current study, the potency and cellular toxicity of four fluoroquinolones (enoxacin, ciprofloxacin, levofloxacin, and moxifloxacin) were assessed in Vero cells and A549 cells engineered to overexpress ACE2, the SARS-CoV-2 entry receptor. All four fluoroquinolones suppressed SARS-CoV-2 replication at high micromolar concentrations in both cell types, with enoxacin demonstrating the lowest effective concentration 50 value (EC₅₀) of 126.4 μM in Vero cells. Enoxacin also suppressed the replication of MERS-CoV-2 in Vero cells at high micromolar concentrations. Cellular toxicity of levofloxacin was not found in either cell type. In Vero cells, minimal toxicity was observed following treatment with ≥37.5 μM enoxacin and 600 μM ciprofloxacin. Toxicity in both cell types was detected after moxifloxacin treatment of ≥300 μM. In summary, these results suggest that the ability of fluoroquinolones to suppress SARS-CoV-2 and MERS-CoV replication in cultured cells is limited. Full article

Repurposing FDA-approved compounds could provide the fastest route to alleviate the burden of disease caused by flaviviruses. In this study, three fluoroquinolones, enoxacin, difloxacin and ciprofloxacin, curtailed replication of flaviviruses Zika (ZIKV), dengue (DENV), Langat (LGTV) and Modoc (MODV) in HEK-293 cells at low micromolar concentrations. Time-of-addition assays suggested that enoxacin suppressed ZIKV replication at an intermediate step in the virus life cycle, whereas ciprofloxacin and difloxacin had a wider window of efficacy. A129 mice infected with 1 × 10⁵ plaque-forming units (pfu) ZIKV FSS13025 (n = 20) or phosphate buffered saline (PBS) (n = 11) on day 0 and treated with enoxacin at 10 mg/kg or 15 mg/kg or diluent orally twice daily on days 1–5 did not differ in weight change or virus titer in serum or brain. However, mice treated with enoxacin showed a significant, five-fold decrease in ZIKV titer in testes relative to controls. Mice infected with 1 × 10² pfu ZIKV (n = 13) or PBS (n = 13) on day 0 and treated with 15 mg/kg oral enoxacin or diluent twice daily pre-treatment and days 1–5 post-treatment also did not differ in weight and viral load in the serum, brain, and liver, but mice treated with enoxacin showed a significant, 2.5-fold decrease in ZIKV titer in testes relative to controls. ZIKV can be sexually transmitted, so reduction of titer in the testes by enoxacin should be further investigated. Full article

Cervical cancer is a major cause of death in females worldwide. While survival rates have historically improved, there remains a continuous need to identify novel molecules that are effective against this disease. Here, we show that enoxacin, a drug most commonly used to treat a broad array of bacterial infections, is able to inhibit growth of the cervical cancer cells. Furthermore, our data show that epigallocatechin gallate (EGCG), a plant bioactive compound abundant in green tea, and known for its antioxidant effects, similarly functions as an antiproliferative agent. Most importantly, we provide evidence that EGCG functions synergistically against cancer cell proliferation in combined treatment with enoxacin. These data collectively suggest that enoxacin and EGCG may be useful treatment options for cases of cervical cancer. Full article

A rapid, simple, and sensitive immunochromatographic test strip has been developed for testing residues of ciprofloxacin (CIP). A specific and sensitive monoclonal antibody (mAb) for CIP was generated by immunizing BALB/c mice with well-characterized CIP-Keyhole limpet haemocyanin. Under the optimized conditions, the cut-off limits of test strips for CIP were found to be 5 ng/mL in phosphate-buffered saline and 2.5 ng/mL in milk samples. Each test can be evaluated within 3 min. The cross-reactivities of the CIP test strip to enrofloxacin (ENR), norfloxacin (NOR), nadifloxacin (NDF), danofloxacin (DANO), pefloxacin (PEX), lomefloxacin (LOME), enoxacin (ENO), and sarafloxacin (SAR) were 71.4%, 71.4%, 66%, 50%, 33%, 20%, 12.5%, and 6.25%, respectively. The data indicate that the method is sensitive, specific, and has the advantages of simplicity and speed, therefore, this test strip is a useful screening method for the detection of CIP residues in milk samples. Full article