The lipophilic derivative of thalidomide (4-(1,3-dioxo-1,3-dihydro-2
-isoindol-2-yl)-
-(4-ethoxyphenyl)methylidenebenzohydrazide,
) was synthesized to enhance its characteristics and efficacy. ...Earlier studies have proved the immunomodulatory and anti-inflammatory effects of
. In this study the interaction between bovine serum albumin (BSA) and
was studied using a multi-spectroscopic approach which included UV spectrophotometry, spectrofluorimetry and three dimensional spectrofluorometric and molecular docking studies. Static quenching was involved in quenching the fluorescence of BSA by
, because a complex formation occurred between the
and BSA. The binding constant decreased with higher temperature and was in the range of 2.5 × 10⁵-4.8 × 10³ L mol
suggesting an unstable complex at higher temperatures. A single binding site was observed and the the site probe experiments showed site II (sub-domain IIIA) of BSA as the binding site for
. The negative values of ∆G⁰, ∆H⁰ and ∆S⁰ at (298/303/308 K) indicated spontaneous binding between
and BSA as well as the interaction was enthalpy driven and van der Waals forces and hydrogen bonding were involved in the interaction. The docking results and the results from the experimental studies are complimentary to each other and confirm that
binds at site II (sub-domain IIIA) of BSA.
The binding interaction between bovine serum albumin (BSA) and roflumilast (ROF) was explored in this study. The binding of drugs to albumin plays a vital role in their pharmacokinetics and ...pharmacodynamics in vivo. The mechanisms involved in the interaction between BSA and ROF was studied using multi-spectroscopic experimental and computational approaches.
Spectrofluorometric experiments were used to determine the method of quenching involved and the conformational changes in the BSA. UV-visible spectroscopy synchronous and three-dimensional fluorescence spectroscopy were used to further explore the binding interaction mechanism.
The results suggested that the intrinsic fluorescence of BSA was quenched due to the formation of a static complex between ROF and BSA. Conformational changes in BSA were determined based on its interaction with ROF. The thermodynamic results suggested that the interaction between ROF and BSA was spontaneous and a hydrophobic interaction occurred between them. Site I of BSA was suggested as the site of interaction between ROF and BSA based on the site marker experiments.
The molecular simulation results and the experimental outcomes were complimentary to each other and helped to identify the binding site and nature of bonds involved in the interaction between ROF and BSA.
The FT-Raman and FT-IR spectra of N-(adamantan-1-yl)-1,2,3,4-tetrahydroisoquinoline-2-carbothioamide were recorded and investigated. The DFT/M06-2X/6-311++G(d,p) method was used to compute the ...vibrational wavenumbers. The effect of solvents (water, carbon tetrachloride and chloroform) on the dipole moment and polarizability has been evaluated. UV–Vis spectrum of the title compound was recorded and compared with the theoretical spectrum calculated by TD-DFT approach. To investigate the movement of electrons within the system when excited, the difference of the excited and ground state densities has also been plotted. The molecular docking studies reveals that the investigated compound may exhibit HIV-1 Protease inhibitory activity.
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•Molecular properties of C20H26N2S, having tetrahydroisoquinoline, carbothiomide and adamantane moieties.•Effect of the solvents on the dipole moment and polarizability has been investigated.•Total electron density difference between ground and excited states have been plotted.•Molecular Docking studies reveal, C20H26N2S as a potential inhibitor of HIV-1 Protease.
The present study describes the development of a novel analytical approach that can reduce by 50-fold the consumption of organic solvents in the charge transfer (CT)-based spectrophotometric ...analysis. The proposed approach employed 96-microwell assay plates for carrying out the reaction. The CT reaction between the electron-donating analyte and electron-accepting reagent was performed in microwells (200-μL of organic solvent) and the color signals were measured with a microwell-plate reader. Optimum conditions for the proposed approach were established for two antihypertensive drugs, namely ramipril (RML) and lisinopril (LSL) as model compounds for the electron-donating analytes, and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) as a π-electron acceptor. Under the optimum conditions, Beer's law was obeyed in the concentration range of 6-100 and 6-60 μg mL-1 for RML and LSL, respectively. The limits of detection were 0.97 and 1.10 μg mL-1 for RML and LSL, respectively. The precision of the methods was satisfactory; the values of relative standard deviations did not exceed 1.1 %. The proposed approach was successfully applied to the analysis of pharmaceutical dosage forms with good accuracy and precision. The results were comparable with those of the reported methods. The approach described herein is of great practical value in pharmaceutical analysis because it reduces the exposure of analysts to the toxic effects of organic solvents, lowers the analysis cost by 50-fold, and it has a high throughput property. Although the approach was validated for RML and LSL, the same methodology could be used for any electron-donating analyte for which a CT-reaction can be performed.
U radu je opisan razvoj novog analitičkog pristupa koji 50 puta smanjuje potrošnju organskih otapala u spektrofotometrijskoj analizi na bazi prijenosa naboja (CT). Predložena metoda koristi ploče s 96 jažica za izvođenje analize. CT reakcije između elektron-donora i elektron-akceptora izvode se u jažicama s 200-μL organskog otapala. Promjene boje mjere se pomoću posebnog mikročitača za ploče s jažicama. Određeni su optimalni uvjeti za dva antihipertenzivna lijeka, ramipril (RML) i lizinopril (LSL) koji su upotrebljeni kao modelni spojevi za elektron-donorske analite, i 2,3-diklor-5,6-dicijano-1,4-benzokinon (DDQ) kao π-elektronski akceptor. U optimalnim uvjetima Beerov zakon je vrijedio u koncentracijskom području 6-100 i 6-60 μg mL-1 za RML, odnosno LSL. Granice detekcije bile su 0,97 i 1,1 μg mL-1 za RML, odnosno LSL. Preciznost metode bila je zadovoljavajuća, a relativna standardna devijacija bila je manja od 1,1 %. Predložena metoda uspješno je primijenjena za analizu doziranih farmaceutskih pripravaka koji sadrže ispitivane lijekove, uz dobru točnost i preciznost. Rezultati predložene metode usporedivi su s rezultatima poznatih metoda. Postupak opisan u ovom radu vrlo je praktičan: analitičari su manje izloženi toksičnim učincima organskih otapala, troškovi analize smanjeni su 50 puta, a također ju odlikuje visoka propusnost. Iako je postupak validiran za RML i LSL, ista metoda može se upotrijebiti za elektron-donirajući analit koji ulazi u CT reakciju.
Losartan: Comprehensive Profile Al-Majed, Abdul-Rahman A; Assiri, Ebrahim; Khalil, Nasr Y ...
Profiles of drug substances, excipients, and related methodology,
2015, Letnik:
40
Journal Article
Recenzirano
Losartan (Cozaar™) is an angiotensin II receptor antagonist with antihypertensive activity. It is used in the management of hypertension and heart failure. Nomenclature, formulae, elemental analysis, ...and appearance of the drug are included in this review. The uses, applications, and the variety of synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum with fragmentation patterns, and NMR (1H and 13C) spectra of losartan together with the corresponding figures and/or tables are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including: spectrophotometric, electrochemical, chromatographic, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior and the pharmacology of the drug are also provided.
A highly sensitive competitive enzyme immunoassay (EIA) has been developed and validated for the determination of the plasma level of 2′-deoxycytidine (dCyd), the potential prognostic marker for ...breast cancer chemotherapy. This assay employed a monoclonal antibody that recognizes dCyd with a high specificity, and 5′-succinyl-dCyd (5′sdCyd) conjugate of bovine serum albumin (5′sdCyd–BSA) immobilized onto microplate wells as a solid phase. The assay involved a competitive binding reaction between dCyd, in plasma sample, and the immobilized 5′sdCyd–BSA for the binding sites of the anti-dCyd antibody. The bound antibody was quantified with horseradish peroxidase-labeled anti-immunoglobulin second antibody and 3,3′,5,5′-tetramethylbenzidine as a peroxidase substrate. The concentration of dCyd in the sample was quantified by its ability to inhibit the binding of the antibody to the immobilized 5′sdCyd–BSA and subsequently the color formation in the assay. The assay limit of detection was 8
nM and the effective working range at relative standard deviations (R.S.D.s) of ≤10% was 20–800
nM. No cross-reactivity from the structurally related nucleobases, nucleosides, and nucleotides was observed in the proposed assay. Mean analytical recovery of added dCyd was 98–100
±
3.2–8.2%. The precision of the assay was satisfactory; R.S.D. was 3.4–4.2 and 4.3–8.9% for intra- and inter-assay precision, respectively. The proposed EIA was compared favorably with HPLC method in its ability to accurately measure dCyd spiked into plasma samples. The analytical procedure is convenient, and one can analyze 200 samples per working day, facilitating the processing of large-number batch of samples. The proposed EIA is expected to contribute in further evaluation of dCyd as a prognostic marker for breast cancer chemotherapy and elucidation of the role of dCyd in various biological and biochemical systems.
Dependence on antipsycotic drugs like aripriprazole (ARI) is increasing at alarming rate, hence, this study was undertaken to support the hypothesis that supplementation of Citrus paradisi ...(Grapefruit) juice having high concentration of polyphenols might potentiate and synergize the therapeutic effect of ARI, by increasing its bioavailability and inherent antioxidant potential. These benefits together might decrease the daily dosage of the ARI and thus alleviate the possible side effects of drug.
In this study the antioxidant and anti-inflammatory potential of ARI alone and in combination with GFJ was evaluated for hydrogen peroxide (H
O
) induced oxidative stress in mice. Seventy mice (4 weeks old), were randomly divided into seven groups. Group I: Control; Group II: H
O
treated; Group III; ARI treated; Group IV GFJ treated; Group V: GFJ and H
O
treated; Group VI; ARI and H
O
treated; Group VII; ARI, GFJ and H
O
treated. Serum levels of alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine kinase (CK), creatinine and total protein were measured. Furthermore, pro-inflammatory cytokines Interleukin (IL)-1α, IL-2, IL-10 and tumor necrosis factor-α (TNF-α) concentrations were also measured.
The mice group that was treated with ARI, GFJ or combination of the two showed significant improvement in the H
O
altered parameters with the combination group showing more significant improvement than the ARI and GFJ alone groups indicating a synergistic and potentiating effect of the antioxidant and anti-inflammatory potential of GFJ on ARI.
Supplementing GFJ to ARI might increase an anti-oxidative potential of ARI due to inherent antioxidant and anti-inflammatory activity of GFJ and thus could alleviate the possible dosage dependent side effects of ARI.
A highly sensitive LC method with column-switching “Co-sense” system and fluorescence detection has been proposed for trace determination of sertraline in human plasma. A simple pre-column ...derivatization procedure with 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole reagent was employed. Fluxetine was used as an internal standard. Under the optimum chromatographic conditions, a linear relationship with good correlation coefficient (r = 0.9997) was found between the peak area ratio and sertraline concentration in the range of 5-5,000 ng mL⁻¹. The limit of detection and limit of quantitation were 1.41 and 4.28 ng mL⁻¹, respectively. The intra- and inter-assay precisions were satisfactory; the relative standard deviations did not exceed 5.63%. The accuracy of the method was proved; the recovery of sertraline from the spiked human plasma was 99.76-102.62 ± 2.19-5.63%. The proposed method had high throughput as the analysis involved simple sample pre-treatment procedure and short run-time (~12 min). The results demonstrated that the method would have a great value if applied in bioavailability and pharmacokinetic studies for sertraline.
Background: The binding interaction between bovine serum albumin (BSA) and roflumilast (ROF) was explored in this study. The binding of drugs to albumin plays a vital role in their pharmacokinetics ...and pharmacodynamics in vivo. The mechanisms involved in the interaction between BSA and ROF was studied using multi-spectroscopic experimental and computational approaches. Materials and methods: Spectrofluorometric experiments were used to determine the method of quenching involved and the conformational changes in the BSA. UV-visible spectroscopy synchronous and three-dimensional fluorescence spectroscopy were used to further explore the binding interaction mechanism. Results: The results suggested that the intrinsic fluorescence of BSA was quenched due to the formation of a static complex between ROF and BSA. Conformational changes in BSA were determined based on its interaction with ROF. The thermodynamic results suggested that the interaction between ROF and BSA was spontaneous and a hydrophobic interaction occurred between them. Site I of BSA was suggested as the site of interaction between ROF and BSA based on the site marker experiments. Conclusion: The molecular simulation results and the experimental outcomes were complimentary to each other and helped to identify the binding site and nature of bonds involved in the interaction between ROF and BSA. Keywords: roflumilast, bovine serum albumin, COPD, fluorescence, quenching
Geochemical study of groundwater from a structurally deformed granitic terrain near Hyderabad (India) was carried out to understand and evaluate the hydrogeochemical processes and quality of ...groundwater. Several trace elements (Fe, Mn, Be, Al, V, Cr, Co, Ni, Cu, Zn, As, Sr, Mo, Cd, Sb, Ba, Pb, U) along with major ions and minor elements were precisely estimated in shallow and drilled wells to know the suitability of water for drinking and irrigation purposes. Analytical data shows that pH and major ion chemistry in dug wells and bore wells do not vary significantly, while some trace elements (Fe, Mn, Al, Be, Co, Pb, U and Zn) vary in dug wells and bore wells, which can be attributed to differential mineral weathering and dissolution/precipitation reactions along fractures/joints. Although the water is not potable, it was found to be suitable for irrigation with little danger in the development of harmful level of exchangeable sodium. It is inferred that the chemical composition of the groundwater in this region is likely to have its origin from silicate weathering reactions and dissolution/precipitation processes supported by rainfall and groundwater flow.
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