Niclosamide Research Articles

Binding interactions of niclosamide with serum proteins

A study of the binding of niclosamide (NC) to serum proteins such as human serum albumin, hemoglobin, and globulin was carried out using fluorescence and UV-visible spectroscopy. Interactions between NC and these proteins were estimated by Stern–Volmer and van't Hoff equations. The binding constants and the thermodynamic parameters, ΔH, ΔS, and ΔG at different temperatures were also determined by using these equations. Data showed that NC may exhibit a static quenching mechanism with all proteins. The thermodynamic parameters were calculated. Data showed that van der Waals interactions and hydrogen bonds are the main forces for human serum albumin and hemoglobin. Globulin, however, bound to NC via hydrophobic interaction. The spectral changes of synchronous fluorescence suggested that both the microenvironment of NC and the conformation of the proteins changed in relation to their concentrations during NC's binding.

Spectrophotometric Determination of Niclosamide by Prior Reduction and Subsequent Diazotization-Coupling with 2,6-Dihydroxybenzoic acid – Application to Tablets

A simple, rapid and sensitive spectrophotometric method is proposed for the determination of niclosamide (NIC) in pure form and in its pharmaceutical preparations. The method is based on the reduction of niclosamide by zinc powder in acidic medium followed by the diazotization of reduced niclosamide, then coupling with 2,6- dihydroxybenzoic acid to give a yellow colored product which is water – soluble and has a maximum absorption at 456 nm with a molar absorptivity of 2.36×104 l.mol-1. cm-1. The color reaction is highly stable and does not show a significant change in absorbance up to 24 hours. Beerُُs law is obeyed in the concentration range of 5–300 µg of niclosamide in a final volume of 10 ml. The method has been successfully applied to the determination of niclosamide in tablets.

Differential pulse striping voltammetric determination of molluscicide niclosamide using three different carbon nanomaterials modified electrodes

Three different carbon nanomaterials modified electrodes based on single(multi)-walled carbon nanotubes (S(M)WCNTs) and electrochemically reduced graphene oxide (ER-GO) modified glassy carbon electrodes (GCE) were fabricated and used to investigate the electrochemical behavior of niclosamide (NA) by cyclic voltammetry and differential pulse anodic stripping voltammetry. Experimental parameters, such as the preconcentration time, scan rate, and the pH value of buffer solution were optimized. A possible working mechanism for the electrochemical detection of NA was also proposed. The electrochemical performances of these three carbon nanomaterials modified electrodes were compared with one another. Among three modified electrodes, ER-GO/GCE displayed lowest peak potential, highest sensitivity, best repeatability, reproducibility and peak shape as well as higher peak current response. Additionally, ER-GO/GCE exhibited better linearity than S(M)WCNTs/GCE over ranges from 0.020 to 23.1μM with the detection limit of 6.6nM (S/N=3), and also successfully employed for real sample analysis with NA tablets. Satisfactory results indicated that ER-GO/GCE can provide a promising candidate for the trace analysis of NA in agriculture.

Sensitive Voltammetric Determination of Niclosamide at a disposable pencil graphite electrode

Niclosamide (NA), an effective drug against tapeworm infections, was electrochemically studied using a pencil graphite electrode (PGE). A low-cost sensitive and selective procedure was developed for determination of NA by recording differential pulse voltammograms of NA in pH 7.0 Britton-Robinson buffer solution containing 0.1M KCl and 30% DMF at the PGE. The PGE displayed very good electrochemical behavior with significant enhancement of the peak current compared to a glassy carbon electrode. Moreover, results obtained from the differential pulse voltammograms show that PGE offers a disposable, low cost, selective and sensitive electrochemical sensor for determination of NA. Under experimental conditions, the PGE had a linear response range from 0.05μM to 10μM NA with a detection limit of 0.015μM (based on 3sb). A relative standard deviation of 0.57% was obtained for five successive determinations of 5μM NA, which indicate acceptable repeatability. This voltammetric method was successfully applied to the direct determination of NA in tablets. No interference from the tablet excipients was encountered.

Niklozamidin Galleria mellonella L. (Lepidoptera: Pyralidae)'nın bazı biyolojik ve fizyolojik özelliklerine etkisi

Salisilanilidler bagirsak seridi gibi parazitlerin mitokondrisinde oksidatif fosforilasyonu inhibe ederek etkisini gosterirler ve bu antiparazitik ilaclar tipta ve veterinerlikte kullanilmaktadir. Niklozamidin potansiyel antihelmintik aktivitesi memelilerde iyi bir sekilde ortaya konulmus, bu calismada da Galleria mellonella larvalari kullanilarak niklozamidin in vivo insektisit etkisi arastirilmistir. Niklozamid, 7. donem larva, pupa ve ergin evrelerinin yasama oranini onemli derecede dusururken, en yuksek konsantrasyonu (% 1,0) ergin gelisme suresini onemli derecede uzatmistir. Disilerin yumurta verimi kontrol besininde 78,6 ± 6,1 yumurta sayisi/gun/disi olarak tespit edilmistir. % 0,1’lik niklozamid ile beslenildiginde ise bu deger 114,7 ± 10,9 yumurta sayisi/gun/disi’ a yukselmistir; bunun yanisira en yuksek konsantrasyonda (% 1,0) hic yumurta elde edilememistir. Niklozamidin en yuksek konsantrasyonunda (% 1,0) erkek ergin omur uzunlugu artmistir. Ayrica, niklozamid yumurta acilimini da denenen tum konsantrasyonlarda onemli oranda dusurmustur. % 0,1’lik niklozamid konsantrasyonunda malondialdehit (MDA) miktari 4 kat, glutatyonS-transferaz enzimi (GST) aktivitesi ise 2 kat artmistir. Kontrol besinine gore (133,24 ± 23,6 nmol/mg protein) niklozamidin denenen konsantrasyonlari protein karbonil (PCO) miktarini en az 5 kat (701,24 - 808,02 nmol/mg protein) onemli derecede arttirmistir. Bu calismada Galleria mellonella model bocek olarak kullanilarak, boceklerle mucadelede belirli klinik oneme sahip antihelmintik ilaclarin aktif sekilde kullanilabilirligi belirtilmistir. Ayrica, bu calismanin sonuclari niklozamidin prooksidan etkisine bagli olarak biyolojik ve ayni zamanda bocegin antioksidan savunma cevabi uzerine negatif etkisi oldugunu gostermistir

Simultaneous determination of niclosamide and its degradates in water by LC-MS/MS

A new method for the analysis of niclosamide (NIC) and its primary degradates 2-chloro-4-nitroaniline (2C4NA), aminoniclosamide (AN), hydroxyniclosamide (HN) and 5-chlorosalicylic acid (5CSA) in environmental water samples was developed using direct injection LC-MS/MS.

Activities of Drug Combinations against Mycobacterium tuberculosis Grown in Aerobic and Hypoxic Acidic Conditions

Mycobacterium tuberculosis is exposed to hypoxia and acidity within granulomatous lesions. In this study, an acidic culture model of M. tuberculosis was used to test drug activity against aerobic 5-day-old (A5) and hypoxic 5-, 12-, and 19-day-old (H5, H12, and H19, respectively) bacilli after 7, 14, and 21 days of exposure. In A cultures, CFU and pH rapidly increased, while in H cultures growth stopped and pH increased slightly. Ten drugs were tested: rifampin (R), isoniazid (I), pyrazinamide (Z), ethambutol (E), moxifloxacin (MX), amikacin (AK), metronidazole (MZ), nitazoxanide (NZ), niclosamide (NC), and PA-824 (PA). Rifampin was the most active against A5, H5, H12, and H19 bacilli. Moxifloxacin and AK efficiently killed A5 and H5 cells, I was active mostly against A5 cells, Z was most active against H12 and H19 cells, and E showed low activity. Among nitrocompounds, NZ, NC, and PA were effective against A5, H5, H12, and H19 cells, while MZ was active against H12 and H19 cells. To kill all A and H cells, A5- and H5-active agents R, MX, and AK were used in combination with MZ, NZ, NC, or PA, in comparison with R-I-Z-E, currently used for human therapy. Mycobacterial viability was determined by CFU and a sensitive test in broth (day to positivity, MGIT 960 system). As shown by lack of regrowth in MGIT, the most potent combination was R-MX-AK-PA, which killed all A5, H5, H12, and H19 cells in 14 days. These observations demonstrate the sterilizing effect of drug combinations against cells of different M. tuberculosis stages grown in aerobic and hypoxic acidic conditions.

Setting up the chromatographic analysis of anthelmintics using the “Crossed D-Optimal” experimental design methodology

An “experimental design” methodology was applied to optimize the chromatographic separation and quantitative determination of six anthelmintics levamisole (LEV), thiabendazole (THI), mebendazole (MEB), albendazole (ALB), praziquantel (PRA) and niclosamide (NICL) by HPLC. Based on the “Crossed D-Optimal” criterion, the participation of three mixed solvents in the mobile phase (methanol, water and acetonitrile) was investigated, since binary systems presented low chromatographic resolution. Furthermore, this approach provides an opportunity to use a crossover design to study the effects of other chromatographic parameters, such as pH, which is considered important for achieving optimal results. Sample analysis was carried out on an HS C18 column (250 × 4.6 mm) 5 μm at 40 °C and the detection was performed with both a UV-diode array detector and an ELSD (Evaporative Light Scattering Detector). The mobile phase consists of an aqueous ammonium acetate buffer (pH 5.5; 0.05 M), acetonitrile and methanol (40 : 37 : 23, v/v/v) with 1 mL min−1 flow rate. The system was found to produce sharp and well resolved peaks for all analytes with their retention times ranging from 3.5 to 13.0 min. Linear regression analysis for the calibration curves showed a good relationship with regression coefficients higher than 0.999 for the UV detector and 0.997 for the ELSD respectively. The proposed method was validated and proven to be accurate, precise, reproducible and suitable for routine analyses.

Laboratory Evaluation of the Molluscicidal Activity of Pulsatilla Chinensis (Bunge) Regel Saponins against the Snail Oncomelania Hupensis

ObjectiveTo observe the toxicity of Pulsatilla chinensis (Bunge) Regel saponins (PRS) against Oncomelania hupensis (O. hupensis). MethodsO. hupensis snails were exposed to 40% and 80% of 24 h LC50 of PRS for 24 h, and then choline esterase (CHE), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) activities in cephalopodium and liver of snails were determined. Niclosamide (NIC) was used as the reference molluscicide. Zebra fish lethality test was evaluated to non-target aquatic species of PRS. ResultsThe molluscicidal activity of PRS (LC50 at 24 h: 0.48 mg/L) was similar to that of NIC (LC50 at 24 h: 0.16 mg/L). Significant alterations about CHE, ALP, and ALT activities both in the cephalopodium and the liver of snails were observed when O. hupensis was exposed to 40% and 80% LC50 of PRS or NIC for 24 h. PRS and NIC could not affect LDH activity in the cephalopodium and the liver. Lower toxicity to fish of PRS was observed up to the highest concentration tested than NIC. ConclusionPRS, as compared with the reference molluscicide NIC, is thought to be used for the control of harmful vector snails safely.

Pharmaceutical Cocrystals of Niclosamide

Niclosamide (NCL) is an anthelmintic BCS class II drug of low solubility and high permeability. Pharmaceutical cocrystals of NCL were prepared with GRAS molecules, such as caffeine (CAF), urea (URE), p-aminobenzoic acid (PABA), theophylline (THPH), nicotinamide (NCT), and isonicotinamide (INA), to improve drug solubility. Neat grinding, wet granulation, and slow evaporation methods were successful to make niclosamide cocrystals. All new crystalline forms were characterized by X-ray diffraction, differential scanning calorimetry, and IR-Raman spectroscopy to confirm their purity and homogeneity. X-ray crystal structures provided details of hydrogen bonding, molecular packing, and drug···coformer interactions. The intermolecular O–H···O hydrogen bond from the hydroxyl donor to the carbonyl acceptor in the niclosamide crystal structure was replaced by an acceptor atom of the coformer in cocrystal structures. Cocrystals with nicotinamide and isonicotinamide were characterized by 13C ss-NMR spectroscopy becaus...

Application of carbon nanoparticle/chitosan modified electrode for the square-wave adsorptive anodic striping voltammetric determination of Niclosamide

A new modified electrode formed by carbon nanoparticle/chitosan film (CNP/CS) was used for electrocatalytic reduction of Niclosamide (NA). The electrochemical behavior of NA at the CNP/CS modified electrode was investigated in detail by the means of cyclic voltammetry. The reduction mechanism of NA, corresponds to the redox chemistry of nitro group, was thoroughly investigated. The effect of the experimental parameters e.g. potential and time of accumulation, pH of the buffered solutions and potential sweep rate on the response of the electrode was studied. The prepared electrode showed high stability and uniformity in the composite film, short response time, good reproducibility and an excellent catalytic activity toward the electro-reduction of NA leading to a significant improvement in response sensitivity. The square-wave adsorptive anodic stripping voltammetry (SWAASV) was used as an efficient method for the determination of NA. Under the optimal conditions, the modified electrode showed a wide linear response to the concentration of NA in the range of 0.01–2 μM with a detection limit of 7.7 nM. The prepared electrode was successfully applied for the determination of NA in pharmaceutical and clinical samples and satisfactory results are obtained.

Comparative molluscicidal action of extract of Ginko biloba sarcotesta, arecoline and niclosamide on snail hosts of Schistosoma japonicum

In search for new local plant molluscicides for the control of the vectors of schistosomiasis, we compared the molluscicidal action of the extract of Ginkgo biloba sarcotesta by benzinum (EGSB) to that of arecoline (ARE) and niclosamide (NIC) against Oncomelania hupensis snails. NIC showed the highest toxicity on snails with 24 h LC 50 vales of 0.12 mg/L and LC 90 of 0.98 mg/L, while the LC 50 and LC 90 of EGSB were much lower than that of ARE. Sublethal in vivo 24 h exposure to 40% and 80% LC 50 of NIC, EGSB and ARE altered the activities of different enzymes in different body tissues of snails. EGSB could significantly inhibit Choline esterase (ChE), Alanine aminotransferase (ALT), Alkaline phosphatase (ALP) and Malic dehydrogenase (MDH) activities both in the cephalopodium and liver. ARE could significantly cause a reduction in ChE, ALP activities in the cephalopodium and ChE, ALT, ALP, Succinodehydrogenase (SDH), MDH activities in the liver. NIC significantly altered activities of ChE, ALT, ALP, SDH, and MDH in the cephalopodium and ChE, ALT, ALP, SDH activities in the liver. All molluscicides could not affect Lactate dehydrogenase (LDH) activity in the cephalopodium and the liver. Maximum inhibition of ALT and MDH activities was found in the cephalopodium and liver of snails treated with 80% of 24 h LC 50 of EGSB. However, NIC and ARE caused maximum reduction in ALP and SDH activities, respectively. The results indicated that molluscicidal action of EGSB was different to that of ARE and NIC in some extent.

Molluscicidal activity of crude water leaf extracts of Alternanthera sesselis on Bulinus (phy) globosus

Evaporated and unevaporated extracts were prepared from both dried and fresh leaves sample and subjected to a 24 h static bioassay. A reference molluscicide niclosamide (Baylusicide) was used as standard and rainwater as untreated control. Reaction of the snails on coming in contact with the test medium is either shock or distress. The distress reaction started with retraction of tentacles and ended in some cases with death. Shock reaction results when snails are immersed in a more concentrated crude water extract which usually resulted in the death of the snails. Statistical analysis of average mortality figures by the use of probit gave LC50 of 40.42 (35.15 – 46.47) for the unevaporated crude water while the evaporated crude water extract had LC50 of 48.07 (42.81 – 54.28) for the dried leaf extract. For the fresh leaves the unevaporated crude water extract had LC50 of 32.57 (27.15 – 39.08) and evaporated crude water gave 45.00 (39.09 – 51.79). This results show that the molluscicidal properties of the leaf extract was dose dependent as mortality increases with the relative increase in concentration of the extract. Furthermore, the bioavailability of the active component is more in the fresh leaves sample when compared to the lethal concentration values of the dried leaves extract and the potential of the crude water extract in integrated schitosomiasis control is discussed. Key words: Alternanthera sesselis, crude water extract, molluscicidal activity, bioavailability, schistomiasis control.

Toxicity of Euphorbia milii Latex and Niclosamide to Snails and Nontarget Aquatic Species

The toxicity of Euphorbia milii molluscicidal latex and niclosamide (NCL) to target snails (Biomphalaria glabrata and Biomphalaria tenagophila) and nontarget aquatic organisms is evaluated. Planorbidae snails were killed by very low concentrations of lyophilized latex (48-h LC50, mg/L: B. glabrata, 0.12; B. tenagophila, 0.09; Helisoma duryi, 0.10). Latex was less toxic (48-h LC50 or EC50, mg/L) to oligochaeta (Tubifex tubifex, 0.31), planktonic crustacea (Daphnia similis, 0.38; C. dubia, 1.07; Artemia sp., 0.93), and fishes (Danio rerio, 0.96; Poecilia reticulata, 1.39), and considerably less toxic to Ampullariidae snails (Pomacea sp., 10.55) and frog tadpoles (Rana catesbeiana, 7.50). Latex (up to 100 mg/L) was not toxic to bacteria (P. putida and V. fischeri), algae (Selenastrum capricornutum and Chlorella vulgaris), and mosquito larvae (Anopheles albitarsis, Aedes aegypti, Aedes fluviatilis). NCL was very toxic (48-h LC50 or EC50, mg/L) to Planorbidae snails (B. glabrata, 0.15, B. tenagophila, 0.13; H. duryi, 0.10), T. tubifex (0.11), crustacea (D. similis, 0.19; Ceriodaphnia dubia, 0.47; Artemia sp. 0.18), fishes (D. rerio, 0.25; P. reticulata, 0.29), R. catesbeiana (0.16), and Pomacea sp. (0.76). NCL was toxic to bacteria, algae (96-h IC50, mg/L: S. capricornutum, 0.34; C. vulgaris, 1.23) and slightly toxic to mosquito larvae. In conclusion, E. milii latex, as compared with the reference molluscicide niclosamide, presents a higher degree of selectivity toward snails which are intermediate hosts of Schistosoma trematodes.

Determination of niclosamide residues in rainbow trout (Oncorhynchus mykiss) and channel catfish (Ictalurus punctatus) fillet tissue by high-performance liquid chromatography.

Bayluscide [the ethanolamine salt of niclosamide (NIC)] is a registered piscicide used in combination with 3-(trifluoromethyl)-4-nitrophenol (TFM) to control sea lamprey populations in streams tributary to the Great Lakes. A high-performance liquid chromatography (HPLC) method was developed for the determination of NIC residues in muscle fillet tissues of fish exposed to NIC and TFM during sea lamprey control treatments. NIC was extracted from fortified channel catfish and rainbow trout fillet tissue with a series of acetone extractions and cleaned up on C(18) solid-phase extraction cartridges. NIC concentrations were determined by HPLC with detection at 360 and 335 nm for rainbow trout and catfish, respectively. Recovery of NIC from rainbow trout (n = 7) fortified at 0.04 microg/g was 77 +/- 6.5% and from channel catfish (n = 7) fortified at 0.02 microg/g was 113 +/- 11%. NIC detection limit was 0.0107 microg/g for rainbow trout and 0.0063 microg/g for catfish. Percent recovery of incurred radioactive residues by this method from catfish exposed to [(14)C]NIC was 89.3 +/- 4.1%. Percent recoveries of NIC from fortified storage stability tissue samples for rainbow trout (n = 3) analyzed at 5 and 7.5 month periods were 78 +/- 5.1 and 68 +/- 2.4%, respectively. Percent recoveries of NIC from fortified storage stability tissue samples for channel catfish (n = 3) analyzed at 5 and 7.5 month periods were 88 +/- 13 and 76 +/- 21%, respectively.

Influence of cyclodextrines on effective mobilities of metabolically important purines and pyrimidines

A kinetic and mechanistic study of the daylight-mediated photooxidation of the multifunctional drug Niclosamide (NSD) was carried out in aqueous solutions. NSD is a frequent contaminant suspended in natural waters. The aqueous dissolution of the practically insoluble NSD was driven by the presence of 2-hydrxypropyl-β-cyclodextrin (HPβCD). The already proposed formation of an inclusion complex between NSD-HPβCD was confirmed through theoretical studies. NSD-nanoencapsulation within the oligosaccharide occurs with a 1:2 stoichiometry, being the drug embedded into a cavity of two HPβCD molecules, in a so called head-to-head orientation.The Reactive Oxygen Species singlet molecular oxygen, superoxide radical anion and hydrogen peroxide, generated through the visible-light absorber sensitizers Riboflavin and Rose Bengal, are effectively intercepted by the encapsulated biocide and contribute to its photodegradation. The overall NSD photooxidation rate, determined through oxygen consumption indicates that the process is relatively highly efficient in the microheterogeneous aqueous media as compared to NSD in MeOH solution, and to phenol (PHE) in pure water. The paradigmatic water-contaminant PHE was taken a as reference in order to evaluate the persistence of the NSD under photosensitized irradiation in aqueous medium. The photooxidation mechanism of NSD is affected by cyclodextrin complexation, due to dynamic limitations, electrostatic interactions and pH changes upon NSD dissolution in aqueous HPβCD. In this sense, the NSD-HPβCD complex can be seen as a sort of nanoreactor that enables the photodegradation of the biocide in water, under daylight conditions.

Spectrophotometric determination of some antiamoebic and anthelmintic drugs with metol and chromium(VI)

A sensitive spectrophotometric method is reported for the determination of tinidazole (TZ), metronidazole (MZ), benzoyl metronidazole (BMZ) or niclosamide (NS) either in pure form or in formulations. This method is based on reduction with zinc dust and hydrochloric acid followed by reaction with metol and potassium dichromate at pH 3.0 ± 0.2 to give a coloured product having maximum absorbance at 720 nm (for TZ, MZ and BMZ) or 530 nm (for NS).