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    Visible spectrophotometric determination of Furosemide in dosage forms following its hydrolysis and Diazo coupling with Chromotropic Acid
    (Nigeria Association of Pharmacists in Academia, 2023) Thomas, O. E.; Adegoke, O. A.; Taiwo-Ojediran, B.
    Background: Several previously reported visible spectrophotometric methods for the quantification of furosemide in dosage forms are fraught with poor specificity due to background absorptivities of other chemical species in the sample matrices. Objective: To develop a simple, sensitive and specific visible spectrophotometric method for the quantitative determination of furosemide in bulk and dosage forms. Method: The new spectrophotometric method was based on acid-hydrolysis of furosemide followed by its diazotization and coupling with chromotropic acid to generate a red adduct. Reactions variables critical to optimal response were established. Various analytical and validation parameters including repeatability, reproducibility and selectivity were also determined. Results: The calibration graph was linear between 8.09 μg/mL to 161.8 μg/mL at 503 nm with a correlation coefficient of 0.992. The Sandell’s sensitivity of the new method was 0.14 μg.cm-2/0.001 A.U. while the limits of detection and quantification were 0.75 and 2.28 μg/mL respectively. The method was accurate and precise with recovery in the range of 102.24–109.92% and intra- and inter-day precision (%RSD) at three different concentrations less than 2.0%. When applied to the analysis of dosage form, there was no statistical difference between the newly developed and official methods. There was no interference from commonly used excipients or background absorptivities in the sample matrices. Conclusion: In comparison with some previously reported colorimetric methods, the new method reliably quantified furosemide over a wider range of concentration and with a superior level of sensitivity. The new method can serve as a reliable alternative to the official method for analysis of furosemide.
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    In vitro cytotoxicity, genotoxicity and apoptoxicity of 8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes using Human Lymphocytes: Experimental and theoretical profiling
    (Taylor & Francis, 2023) Thomas, O. E.; Adegoke, O. A.; Mukherjee, A.; Banerjee, R.
    Regulatory agencies require demonstration of non-genotoxicity of new chemical entities prior to their use as pharmaceuticals or additives. Consequently, the in vitro cytotoxicity, genotoxicity and apoptoxicity of five novel monoazo colourants (8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes, 3a-e) on human lymphocytes were evaluated using a cell viability assay, alkaline comet assay, DNA diffusion assay, DFT calculations and molecular docking. The test concentrations of the compounds varied from 0 to 3.4 mM. Relative to negative control, the compounds at concentrations up to 0.5mM induced small dose-dependent reduction (< 20%) in viability of lymphocytes. Statistically significant changes (p<0.05) in DNA damage parameters (percent tail DNA, tail extent moment, olive tail moment) were observed at all concentrations of 3a, 3b while 3c-e showed genotoxicity at 2.8, 0.17 and 3.4 mM respectively. Compounds 3a, 3b, 3d induced apoptosis at concentrations below cytotoxic doses while 3c and 3e were non-apoptoxic at all test concentrations. DFT calculations showed the genotoxicity of 3a-e increased with electrophilicity and ionization potentials of the compounds. Molecular docking of 3a-e with apoptosis-associated proteins revealed binding affinity patterns that were consistent with observed experimental apoptoxicity. The structure-genotoxicity relationships of five novel monoazo compounds, which can be employed in the design of safer congeners, have been elucidated.
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    Characterization, antimicrobial and catalytic activities of silver nanoparticles biosynthesized using Aqueous extract of Euphorbia graminea
    (Istanbul Medipol University, 2023) Thomas, O. E.; Alabi, S. O.; Osharode, P.E.
    Phytosynthesis of silver nanoparticles (AgNPs) is not only affordable and ecofriendly but provides a means of synthesizing phytochemical capped AgNPs with predefined characteristics. The objective of this study was the green synthesis of AgNPs that possess antimicrobial and catalytic activities using aqueous extract of Euphorbia graminea. Reactions parameters critical to the yield, size and morphology of the biosynthesized AgNPs were optimized using UV spectroscopy. The UV-visible spectra analysis of the biosynthesized AgNPs showed surface plasmon resonance occurred at 462 nm. Scanning Electron Microscopy with Energy dispersive X-ray analysis revealed the characteristic absorption band of AgNPs at 3 KeV and confirmed 73.66% composition of particles as metallic silver. The AgNPs appeared as well-separated, quasi-spherical particles with narrow size distribution of 6.77±0.89 nm when examined with Transmission electron microscopy. X-ray diffraction confirmed the crystallinity of the AgNPs with mean crystallite size of 7.65 nm. The biosynthesized AgNPs showed broad-spectrum antimicrobial activity against bacteria and fungi. The rate constant of the degradation of methylene blue in the presence of as-synthesized AgNPs was increased several folds to sec-1 from sec-1 in its absence. The prepared AgNPs could find applications as therapeutic.
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    Comparison of the Calf Thymus DNA Binding Interactions of 5-hydroxymethylfurfural and its Synthesized Derivative, 5, 5’[oxy-bis(methylene)]bis-2-furfural: Experimental, DFT and Docking Studies.
    (Taylor & Francis, 2023) Thomas, O. E.; Oduwole, R. T.; Akin-Taylor, A.
    In this study, the in vitro DNA-binding interactions of the food/drug additive, 5-hydroxymethylfurfural (HMF) and its major degradant, 5, 5’[oxy-bis(methylene)]bis-2-furfural (OBMF) were investigated. OBMF was synthesized and characterized using IR, NMR and mass spectrometry. Photometric titrations revealed OBMF induced more extensive perturbations in the 258nm band of DNA and exhibited binding constants that were 5–12-folds higher than those of HMF. The greatest net changes in viscosity of DNA induced by HMF and OBMF were 10.5 and 8.9%, respectively which confirmed both compounds as minor groove binders. Docking revealed that OBMF and HMF bound to the guanine–cytosine regions of minor groove of DNA with global binding energies of −36.36 and −26.12 kcal/mol, respectively. DFT calculations revealed the higher electrophilicity of OBMF contributed to its increased interaction with the negatively charged DNA backbone. There is a need for stricter control of permissible levels of OBMF in food and drug products.
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    Molecular docking and ADMET studies of the Interaction of 4-carboxyl-2,6-dinitrophenylazohydroxynaphthalenes with Bovine Serum Albumin
    (Faculty of Pharmaceutical Sciences, University of Jos, Nigeria., 2023) Thomas, O.E.
    Previous spectrophotometric investigations revealed strong binding affinities between four potential monoazo colourants (code-named AZ-01 to 04) and bovine serum albumin (BSA) which could dictate the tissue distribution and toxicity of the additives. The molecular docking interactions of the dyes with BSA were analyzed using AutoDock vina and PatchDock in order to elucidate the functional groups involved in complex stabilization. Docking conformations confirmed the ligands preferentially inserted into the hydrophobic cavities of BSA site I. Structure-BSA binding relationships revealed the binding of AZ-02 was driven by hydrogen bond donation from its free phydroxynaphthalene substituent to Ser-479 while the predominantly hydrazone form of its positional isomer, AZ-01, increased its lipophilicity and tendency for hydrophobic interactions. The relatively higher C/H ratio of AZ-03 and -04, which contain additional C-7 substituents, was responsible for their stronger binding and the extensive involvement of their aromatic rings in ligand-site I complex stabilization via Pi-Pi T-shaped, Pi-alkyl and alkyl-alkyl interactions. Moreso, AZ-01, -03 and -04 exist predominantly as hydrazone tautomers with an overall positive charge which provided complementary modes for interaction with negatively charged aspartic and glutamic acids. The structure-BSA binding relationships of the molecules, which can be employed in synthesis of safer congeners, have been elucidated.
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    Spectroscopic, molecular docking and semi-empirical studies of the Albumin binding activities of 5-Hydroxymethylfurfural and its synthesized derivative, Di (5-Furfural) Ether
    (Sami Publishing Company, 2022) Thomas O. E.; Oduwole R.
    Previous studies have investigated the safety of the food/drug additive, 5-hydroxymethylfurfural including its albumin binding which might impact on its biodistribution and toxicity. In contrast, the safety assessment of its major degradant, di (5-furfural) ether (OMBF) is often neglected despite having been detected at concentrations in excess of HMF in parenteral solutions. The aim of this study was to compare the albumin binding characteristics of OMBF with 5-hydroxymethylfurfural. OMBF was synthesized by thermal dehydration of 5-hydroxymethylfurfural and characterized by using spectroscopic and mass spectral techniques. The binding characteristics of 5-hydroxymethylfurfural and OMBF with bovine serum albumin (BSA) were elucidated by using UV-visible spectroscopy, molecular docking, and semi-empirical calculations. Photometric titrations with OMBF revealed more pronounced perturbations in the UV-visible spectra of BSA and binding constants that were 51% greater than those of 5-hydroxymethylfurfural. Thermodynamic parameters revealed that the OMBF binding to albumin was spontaneous and hydrophobic interactions were the main forces responsible for complex stabilization. Docking studies showed that the superior binding affinity of OMBF was due to its higher C/H ratio which facilitated an extensive network of six hydrophobic interactions with Tyr149, Leu237, Ala290, Ile289, and Arg194 residues of BSA Site I compared with only two hydrophobic interactions in 5-hydroxymethylfurfural complex. Analysis of the multi-point hydrogen bonded complexes by using PM6-D3H+ method revealed the interaction energy of OMBF-BSA complex was 1.5 folds greater than 5-hydroxymethylfurfural-BSA. The study confirmed an increased avidity and stability in the complexation of albumin with OMBF compared with 5-hydroxymethylfurfural. Stricter limits control of OMBF in heatprocessed foods/drugs is necessary.
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    Phytosynthesis, Antimicrobial and Catalytic Activities of Silver Nanoparticles derived using Leaf and Stem Extracts of Indigofera macrophylla
    (Nigeria Association of Pharmacists in Academia, 2022) Thomas, O. E.; Adegoke, O. A.; Adeniyi, E. M.; Oliver, C. G.
    Background: The phytosynthesis of metal nanoparticles is a promising green alternative to traditional chemical approaches. Objective: The aim of this study was to synthesize silver nanoparticles (AgNPs) with antimicrobial and biocatalytic activities using aqueous leaf and stem extracts of Indigofera macrophylla. Methods: Critical reaction variables for the biosynthesis of AgNPs were optimized using UV-vis spectroscopy before the biosynthesised AgNPs were characterized using various spectroscopic and microscopic techniques. The biological activities of the biogenic nanoparticles were then investigated with particular focus on their antimicrobial activity and biocatalytic efficiency in the degradation of methylene blue. Results: The surface plasmon resonance of silver nanoparticles biosynthesized using aqueous extracts of leaf (LEAgNPs) and stem (SE-AgNPs) of I. macrophylla occurred at 430 and 426 nm respectively. Scanning electron microscopy images of the nanoparticles showed highly aggregated polymorphs with mostly spherical shape. The particle sizes of LE-AgNPs and SE-AgNPs as determined by Transmission electron microscopy were 48.61±8.60 and 18.09±4.13 nm respectively with Energy dispersive X-ray analysis confirming characteristic absorption band at 3 KeV. In susceptibility assays, LE-AgNPs showed dose-dependent zones of inhibition against Escherichia coli (18mm), Staphylococcus aureus (18 mm), Pseudomonas aeruginosa (20 mm) while SE-AgNP was only active against Staphylococcus aureus (10 mm). Both LE-AgNPs and SE-AgNPs showed good biocatalytic efficiency in the degradation of methylene blue with rate constants of 0.0204 and 0.0182 min-1 respectively. Conclusion: Silver nanoparticles with antimicrobial and catalytic activities have been biosynthesized using the aqueous extract of Indigofera macrophylla.
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    Synthesis, characterization and solvatochromic behaviour of new water-soluble 8-hydroxy-3,6-disulphonaphthyl azohydroxynaphthalenes
    (Taylor & Francis, 2022) Thomas O.E.; Adegoke, O.A.
    A series of five tetracyclic mono azo dyes based on the diazotization of 1-amino-8-hydroxynaphthalene-3,6-disulphonic acid and subsequent coupling with substituted (un)sulphonated naphthalene derivatives have been synthesized. The chemical structures of the dyes were established using UV–visible, IR, NMR as well as mass spectrometry. Based on the number of sulphonic acid and other hydrophilic groups they contain, the compounds showed varying extent of water solubility. Spectroscopic characterization revealed the existence of azohydrazone tautomerism and the influence of the structures of solvating solvents on the equilibrium. Statistical analysis of single, dual and multiparametric equations of Kamlet Abboud and Taft parameters showed that solvent polarity was the most significant contributor to the observed spectral patterns of the dyes in pure solvents. The compounds could find useful applications as solvatochromic probes, food and drug colour additives.
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    Preferential solvation of 4-carboxyl-2, 6-dinitrophenylazohydroxynaphthalenes in mixed hydroxylic solvents
    (Nigeria Association of Pharmacists in Academia, 2021) Thomas, O. E.; Adegoke, O. A.; Adenmosun, F. G.; Abiodun, O. J.
    Background: The applications of a group of 4-carboxyl-2,6-dintrophenylazohydroxynaphathalenes, AZ-01 to 04, as colourants, chemosensors or synthetic intermediates have been limited by their solubility. Aim: To investigate the effect of solvent mixture composition on the solubility, solution thermodynamics and position of equilibrium processes of the dyes. Method: The UV-visible spectral patterns of the dyes in binary mixtures including Methanol:Water, Ethanol:Water, Methanol:Ethanol, Methanol:Propan-1-ol, Methanol:Propan-2-ol, Propan-1-ol:Water and Propan-2-ol:Water were acquired. The type and quantitative estimation of solute-solvent interactions at play were determined by fitting spectral patterns to solvent parameters using multilinear regression. Results: Preferential solvation was detected by the non-ideality of the plots of E12 as against the mole fractions of cosolvent in all binary mixtures. In pure solvents, the spectral shifts of AZ-01, 03 and 04, which exist predominantly in the hydrazone form, were affected by polarity of solvent milieu while solvent basicity and acidity, in that order, were the significant parameters for AZ-02. In aqueous alcoholic mixtures, solvent polarity was contributory, although to different degrees, to the observed spectral data of the four dyes. However, solvent acidity and basicity were the primary determinants of spectral shifts observed with AZ-04 and AZ-03 respectively. Spectra-structure relationships identified the formation of the charged hydrazone tautomer which requires stabilisation by polar solvent milieu as responsible for the observed trend. In addition, interactions between new aggregated solvent-solvent species and the propionic acid substituent present in AZ-03 contributed to its spectral shifts. Conclusion: The solvatochromic properties of the phenylazonaphthalene series in binary mixtures have been successfully studied.
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    Heavy Metal Contamination of Paediatric Paracetamol and Ascorbic Acid Drug Products in South-West Nigeria.
    (West African Postgraduate College of Pharmacists (WAPCP), 2019) Thomas, O. E.; Itopa, M. O.; Adegoke, O. A.
    Background: Water is a primary contributor to human populations’ heavy metals exposure and industrial contamination of products. Consequently, paediatric medications because of their high-water constitution can contribute significantly to intake of heavy metals in excess of allowable limits. There is therefore a need for effective preventive and control strategies. Unfortunately, studies investigating heavy metal content in paediatric formulations in Nigeria are scarce and often limited in the range of elements assayed. Objective: To evaluate elemental impurities in the two most frequently administered paediatric medications-paracetamol and ascorbic acid marketed in South-west Nigeria. Methods: Thirteen paediatric syrup brands were used for the study. Sample pretreatment involved dry ashing followed by digestion using concentrated aqua regia (nitric acid:hydrochloric acid, 3:1). Chromium, lead, copper, cadmium, zinc, nickel, cobalt and manganese were assayed with the atomic absorption spectrophotometer with the limit of detection set at 0.001. Results: The most abundant metal ions present in all the formulations were chromium (1.16-1290.2 mg/) and nickel (2.37-1289.0 mg/L). Cadmium was detected at low concentration in only two of the brands while lead was detected in three brands at concentrations ranging from 0.09 - 0.12 mg/L. The calculated expected daily exposures of lead in the three brands were in excess of the permissible daily exposure for oral drug products. Conclusion: Some of the paracetamol and vitamin C syrups sold in the South-West of Nigeria are contaminated with cadmium, nickel and lead.