Department of Chemistry

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    Synthesis and Biological Properties of Ferrocenyl and Organic Methotrexate Derivatives
    (ACS Omega, 2024) Rózga, K.; Błauz, A.; Ayine-Tora, D.M.; et al.
    Synthesis and biological activity of two series of modified side chain methotrexate (MTX) derivatives are presented, one with a ferrocenyl moiety inserted between the pteroyl and glutamate portions of the molecule and the other with glutamate substituted for short chain amino acids. Ferrocenyl derivatives of MTX turned out to be rather moderate inhibitors of dihydrofolate reductase (DHFR) although molecular modeling suggested more effective interactions between these compounds and the target enzyme. More interestingly, ferrocene-decorated MTX derivatives were able to impede the proliferation of four murine and human cell lines as well as their methotrexate-resistant counterparts, overcoming the multidrug resistance (MDR) barrier. They were also able to directly interact with Abcc1, an MDR protein. Of the amino acid pteroyl conjugates, the γ-aminobutyric acid derivative was an efficient inhibitor of DHFR but had no effect on cell proliferation in the concentration range studied while a taurine conjugate was a poor DHFR inhibitor but able to affect cell viability. We postulate that modification of the methotrexate side chain may be an efficient strategy to overcome efflux-dependent methotrexate resistance.
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    Purpose This study aims to examine the effects of cyberbullying on the academic lives of Ghanaian university students. It also establishes whether cyberbullying victims, perpetrators, victim-perpetrators and bystanders differed in their thoughts on the effects of cyberbullying on students’ academic lives. Design/methodology/approach This study is anchored on Bandura’s theory of triadic reciprocal determinism and Abraham Maslow’s theory of needs. This study uses a cross-sectional survey design and quantitative approach to collect the data from 1,374 students from three public universities. The authors use descriptive statistics and ANOVA techniques to analyse the data. Findings The results show that the effects of cyberbullying on academic life are difficulty concentrating on studies, difficulty studying in groups and difficulty assessing important academic information online. There is also a statistically significant difference among cyberbullying victims, perpetrators, victim-perpetrators and bystanders in their thoughts on the effects of cyberbullying on students’ academic lives.
    (Journal of Molecular Structure, 2024) Abbasi, M.A.; Siddiqui, S.S.; Ayine-Tora, D.M.; et al.
    In the research delineate herein, an innovative sequence of new series of multi-functional target molecules (9a-i) having indole-N-phenyltriazole bi-heterocyclic hybrids unified with N-arylated butanamides was synthesized as alkaline phosphatase inhibitor. The structural validation of all the formulated compounds was accomplished through IR, EI-MS, 1 H NMR, 13C NMR and CHN analysis data. The in vitro enzyme inhibitory investigation revealed the efficacy of these bi-heterocyclic derivatives, 9a–i, as potent inhibitors of alkaline phosphatase relative to the standard used. The compound 9h was found to be the most active compound (IC50 = 0.062 ± 0.017 μM), and its inhibitory activity is about 10 times higher than potassium dihydrogen phosphate (KH2PO4) (IC50 = 5.251 ± 0.468 μM). The kinetics mechanism was attributed by evaluating the Lineweaver–Burk plots, which revealed that compound 9h inhibited the alkaline phosphatase non-competitively to form an enzyme –inhibitor complex. The inhibition constant Ki determined from Dixon plots for this compound was 0.045 μM. The computational study was in full agreement with the experimental records and these ligands exhibited good interactions and binding energy values. These molecules also demonstrated mild cytotoxicity toward red blood cell membranes when analyzed through hemolysis. So, based on the presented results, these molecules, being the promising inhibitors of alkaline phosphatase, might be deliberated as suitable medicinal scaffolds to render normal calcification of bones and teeth.
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    Innovations and modifcations of current extraction methods and techniques of citrus essential oils: a review
    (Discover Applied Sciences, 2024) Brah, A.S.; Obuah, C.; Adokoh, C.K.
    The genus Citrus of the Rutaceae family remains one of the benefcial fruit crops that produce high quantities of essential oils that have pharmaceutical, biological, and food preservative applications. Despite the numerous benefts of citrus essential oils (CEOs), there is a major challenge in choosing the most efcient extraction method(s) for large-scale pro duction of quality CEOs to meet industrial, research, and domestic demands. This review provides a general overview of the listed citrus species, the chemical composition of their essential oils, medicinal uses, and the major methods of extraction of citrus essential oils from 10 selected citrus species. A meticulous, in-depth review of the various methods of CEOs extraction has been provided, along with their advantages, limitations, and novel modifcations. This compre hensive literature review expounded on the current extraction methods for citrus essential oils and the various modi fcations developed to reduce the extraction time, excessive energy consumption, CO2 production, and quality, as well as to improve the extraction yield.
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    LiNi1/3Mn1/3Co1/3O2/graphite cells adopting polyolefin and non-polyolefin separators for potential application in industrial manufacturing of energy storage devices
    (Electrochemistry Communications, 2024) Hamenu, L.; Mohammed, L.; Abdul-Samii, R.; et al.
    This study features comprehensive physical and electrochemical properties of different polyolefin and non polyolefin separators. These separators include polypropylene-polyethylene-polypropylene (PEP), polyethylene (PE), Al2O3-coated polypropylene (C-PP), polyethylene terephthalate (PET), and Silicon carbide mat (SiCmat). The interaction of the different separators and the electrolyte was investigated in terms of ionic conductivity, contact angle test, electrolyte uptake, and electrolyte oxidation. The full cells fabricated using the different separators were also studied for charge–discharge performance, cycle performance, and internal resistance. Results showed that the different separators demonstrated different physical and electrochemical behavior. The non-polyolefin separators registered a small electrolyte contact angle due to their high porosity and structural compatibility with the electrolyte. At 10 C-Rate, the specific capacity is in the order of PET > SiCmat > C-PP > PE > PEP corresponding to 90 mAh/g, 85 mAh/g, 70 mAh/g, 60 mAh/g and 40 mAh/g respectively. After 100 cycles at 1.0 C-rate, the cycle performance is in the order of PE > PET > C-PP > SiCmat > PEP corresponding to 70 %, 65 %, 61 %, 51 % and 49 % respectively. Thermally, PET, C-PP and SiCmat showed better thermal stability compared to the other separators. Therefore, Industrial production that requires high thermal stability may rely on C-PP, PET, or SiCmat, while PET and SiCmat offer better cycle performance and may replace commercially available PE and PEP.
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    In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds
    (Int. J. Mol. Sci., 2023) Broni, E.; Ashley, C.; Sakyi, P.O.; et al.
    Adenosine deaminase acting on RNA 2 (ADAR2) is an important enzyme involved in RNA editing processes, particularly in the conversion of adenosine to inosine in RNA molecules. Dysregulation of ADAR2 activity has been implicated in various diseases, including neurological disorders (including schizophrenia), inflammatory disorders, viral infections, and cancers. Therefore, targeting ADAR2 with small molecules presents a promising therapeutic strategy for modulating RNA editing and potentially treating associated pathologies. However, there are limited compounds that effectively inhibit ADAR2 reactions. This study therefore employed computational approaches to virtually screen natural compounds from the traditional Chinese medicine (TCM) library. The shortlisted compounds demonstrated a stronger binding affinity to the ADAR2 (<−9.5 kcal/mol) than the known inhibitor, 8-azanebularine (−6.8 kcal/mol). The topmost compounds were also observed to possess high binding affinity towards 5-HT2CR with binding energies ranging from −7.8 to −12.9 kcal/mol. Further subjecting the top ADAR2–ligand complexes to molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations revealed that five potential hit compounds comprising ZINC000014637370, ZINC000085593577, ZINC000042890265, ZINC000039183320, and ZINC000101100339 had favorable binding free energies of −174.911, −137.369, −117.236, −67.023, and −64.913 kJ/mol, respectively, with the human ADAR2 protein. Residues Lys350, Cys377, Glu396, Cys451, Arg455, Ser486, Gln488, and Arg510 were also predicted to be crucial in ligand recognition and binding. This finding will provide valuable insights into the molecular interactions between ADAR2 and small molecules, aiding in the design of future ADAR2 inhibitors with potential therapeutic applications. The potential lead compounds were also profiled to have insignificant toxicities. A structural similarity search via DrugBank revealed that ZINC000039183320 and ZINC000014637370 were similar to naringin and naringenin, which are known adenosine deaminase (ADA) inhibitors. These potential novel ADAR2 inhibitors identified herein may be beneficial in treating several neurological disorders, cancers, viral infections, and inflammatory disorders caused by ADAR2 after experimental validation
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    Bioaccessibility and children health risk assessment of soil-laden heavy metals from school playground and public parks in Accra, Ghana
    (Springer Link, 2023) Kyene, M.O.; Gbeddy, G.; Mensah, T.; et al.
    Parks and playground soils constitute a critical matrix for children exposure to hazardous substances due to their high exposure rate. However, minimal investigation has been conducted in Ghana on the subject, thus the need for this research. One hundred and twenty (120) soil samples were collected between April 2015 and March 2016 and then analyzed for heavy metals using atomic absorption spectroscopy. The health risk posed to school children by the heavy metals laden in soil was assessed via oral bioaccessibility and hazard index. The oral bioaccessibility of the metals was estimated using the simple bioaccessibility extraction test (SBET) method. Iron (Fe) measured the highest range of total metal concentrations of 2785.0–15275.0 mg kg−1 followed by Pb of 2.1–284.0 mg kg−1. The oral bioaccessibility of the metals varied significantly with Pb and Cu exhibiting the highest mean values of 47.80% and 54.45%, respectively. The sequence for the mean bioaccessibility result does not correspond with the mean concentration of metals in the soil. The hazard index (HI) for most of the heavy metals indicated no potential non-carcinogenic health risk to children (HI < 1) except for Pb. The prolonged use of leaded fuel in Ghana prior to its outright ban on January 1 2004 and the persistence of Pb in soil media may account for its high risk. The deleterious health effects of Pb on children call for the adoption and implementation of appropriate environmental management of playgrounds so as to mitigate children’s exposure to soil-laden heavy metals.
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    In Silico Discovery of Potential Inhibitors Targeting the RNA Binding Loop of ADAR2 and 5-HT2CR from Traditional Chinese Natural Compounds
    (International Journal o f Molecular Sciences, 2023) Broni, E.; Ashley, C.; Sakyi, P.O.; et al
    Adenosine deaminase acting on RNA 2 (ADAR2) is an important enzyme involved in RNA editing processes, particularly in the conversion of adenosine to inosine in RNA molecules. Dysregulation of ADAR2 activity has been implicated in various diseases, including neurological disorders (including schizophrenia), inflammatory disorders, viral infections, and cancers. Therefore, targeting ADAR2 with small molecules presents a promising therapeutic strategy for modulating RNA editing and potentially treating associated pathologies. However, there are limited compounds that effectively inhibit ADAR2 reactions. This study therefore employed computational approaches to virtually screen natural compounds from the traditional Chinese medicine (TCM) library. The shortlisted compounds demonstrated a stronger binding affinity to the ADAR2 (<􀀀9.5 kcal/mol) than the known inhibitor, 8-azanebularine (􀀀6.8 kcal/mol). The topmost compounds were also observed to possess high binding affinity towards 5-HT2CR with binding energies ranging from 􀀀7.8 to 􀀀12.9 kcal/mol. Further subjecting the top ADAR2–ligand complexes to molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations revealed that five potential hit compounds comprising ZINC000014637370, ZINC000085593577, ZINC000042890265, ZINC000039183320, and ZINC000101100339 had favorable binding free energies of 􀀀174.911, 􀀀137.369, 􀀀117.236, 􀀀67.023, and 􀀀64.913 kJ/mol, respectively, with the human ADAR2 protein. Residues Lys350, Cys377, Glu396, Cys451, Arg455, Ser486, Gln488, and Arg510 were also predicted to be crucial in ligand recognition and binding. This finding will provide valuable insights into the molecular interactions between ADAR2 and small molecules, aiding in the design of future ADAR2 inhibitors with potential therapeutic applications. The potential lead compounds were also profiled to have insignificant toxicities. A structural similarity search via DrugBank revealed that ZINC000039183320 and ZINC000014637370 were similar to naringin and naringenin, which are known adenosine deaminase (ADA) inhibitors. These potential novel ADAR2 inhibitors identified herein may be beneficial in treating several neurological disorders, cancers, viral infections, and inflammatory disorders caused by ADAR2 after experimental validation.
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    Design, Synthesis, and Evaluation of Biological Activity of Ferrocene-Ispinesib Hybrids: Impact of a Ferrocenyl Group on the Antiproliferative and Kinesin Spindle Protein Inhibitory Activity
    (Chemistry—A European Journal, 2023) Kowalczyk, K.; Błauż, A.; Ayine-Tora, D.M.; Hartinger, C.G.; et al.
    With the aim to combine more than one biologically-active component in a single molecule, derivatives of ispinesib and its (S) analogue were prepared that featured ferrocenyl moieties or bulky organic substituents. Inspired by the strong kinesin spindle protein (KSP) inhibitory activity of ispinesib, the compounds were investigated for their antiproliferative activity. Among these compounds, several derivatives demonstrated significantly higher antiproliferative activity than ispinesib with nanomolar IC50 values against cell lines. Further evaluation indicated that the antiproliferative activity is not directly correlated with their KSP inhibitory activity while docking suggested that several of the derivatives may bind in a manner similar to ispinesib. In order to investigate the mode of action further, cell cycle analysis and reactive oxygen species formation were investigated. The improved antiproliferative activity of the most active compounds may be assigned to synergic effects of various factors such as KSP inhibitory activity due to the ispinesib core and ability to generate ROS and induce mitotic arrest.
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    Antimicrobial and in silico studies of the triterpenoids of Dichapetalum albidum
    (Heliyon, 2023) Chama, M.A.; Dziwornu, G.A.; Mas-Claret, E.; et al.
    Here we report a new polyhydroxylated triterpene, 2β,6β,21α-trihydroxyfriedelan-3-one (4) iso lated from the root and stem bark of Dichapetalum albidum A. Chev (Dichapetalaceae), along with six known triterpenoids (1–3, 5, 6, 8), sitosterol-3β-O-D-glucopyranoside (9), a dipeptide (7), and a tyramine derivative of coumaric acid (10). Friedelan-3-one (2) showed an antimicrobial activity (IC50) of 11.40 μg/mL against Bacillus cereus, while friedelan-3α-ol (1) gave an IC50 of 13.07 μg/ mL against Staphylococcus aureus with ampicillin reference standard of 19.52 μg/mL and 0.30 μg/ mL respectively. 3β-Acetyl tormentic acid (5) showed an IC50 of 12.50 μg/mL against Trypano soma brucei brucei and sitosterol-3β-O-D-glucopyranoside (9) showed an IC50 of 5.06 μg/mL against Leishmania donovani with respective reference standards of IC50 5.02 μg/mL for suramin and IC50 0.27 μg/mL for amphotericin B. Molecular docking of the isolated compounds on the enzyme glucose-6-phosphate dehydrogenase (G6PDH) suggested 3β-acetyl tormentic acid (5) and sitosterol-3β-O-D-glucopyranoside (9) as plausible inhibitors of the enzyme in accordance with the experimental biological results observed.
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    Alternative boronic acids in the detection of Mycolactone A/B using the thin layer chromatography (f-TLC) method for diagnosis of Buruli ulcer
    (BMC Infectious Diseases, 2023) Akolgo, G.A.; Partridge, B.M.; Craggs, T.D.; Amewu, R.K
    Background Mycobacterium ulcerans is the causative agent of Buruli ulcer. The pathology of M. ulcerans disease has been attributed to the secretion of a potent macrolide cytotoxin known as mycolactone which plays an important role in the virulence of the disease. Mycolactone is a biomarker for the diagnosis of BU that can be detected using the fuorescent-thin layer chromatography (f-TLC) technique. The technique relies on the chemical derivatization of mycolactone A/B with 2-naphthylboronic acid (BA) which acts as a fuorogenic chemosensor. However, back ground interferences due to co-extracted human tissue lipids, especially with clinical samples coupled with the subjectivity of the method call for an investigation to fnd an alternative to BA. Methods Twenty-six commercially available arylboronic acids were initially screened as alternatives to BA using the f-TLC experiment. UV–vis measurements were also conducted to determine the absorption maximum spectra of mycolactone A/B and myco-boronic acid adducts followed by an investigation of the fuorescence-enhancing ability of the boronate ester formation between mycolactone A/B and our three most promising boronic acids (BA15, BA18, and BA21). LC–MS technique was employed to confrm the adduct formation between mycolactone and boronic acids. Furthermore, a comparative study was conducted between BA18 and BA using 6 Polymerase Chain Reaction (PCR) confrmed BU patient samples. Results Three of the boronic acids (BA15, BA18, and BA21) produced fuorescent band intensities superior to BA. Complexation studies conducted on thin layer chromatography (TLC) using 0.1 M solution of the three boronic acids and various volumes of 10 ng/µL of synthetic mycolactone ranging from 1 µL – 9 µL corresponding to 10 ng – 90 ng gave similar results with myco-BA18 adduct emerging with the most visibly intense fuorescence bands. UV–vis absorption maxima (λmax) for the free mycolactone A/B was observed at 362 nm, and the values for the adducts myco-BA15, myco-BA18, and myco-BA21 were at 272 nm, 270 nm, and 286 nm respectively. The comparable experi mental λmax of 362 nm for mycolactone A/B to the calculated Woodward-Fieser value of 367 nm for the fatty acid side chain of mycolactone A/B demonstrate that even though 2 cyclic boronates were formed, only the boronate of the southern side chain with the chromophore was excited by irradiation at 365 nm. Fluorescence experiments have demonstrated that coupling BA18 to mycolactone A/B along the 1,3-diols remarkably enhanced the fuores cence intensity at 537 nm. High-Resolution Mass Spectrometer (HR-MS) was used to confrm the formation of the myco-BA15 adduct. Finally, f-TLC analysis of patient samples with BA18 gave improved BA18-adduct intensities compared to the original BA-adduct. Conclusion Twenty-six commercially available boronic acids were investigated as alternatives to BA, used in the f-TLC analysis for the diagnosis of BU. Three (3) of them BA15, BA18, and BA21 gave superior fuorescence band intensity profles. They gave profles that were easier to interpret after the myco-boronic acid adduct formation and in experi ments with clinical samples from patients with BA18 the best. BA18, therefore, has been identifed as a potential alternative to BA and could provide a solution to the challenge of background interference of co-extracted human tissue lipids from clinical samples currently associated with the use of BA.