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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.
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.
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.
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.
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
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.
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.
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.
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.
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.
Differential constituents in roots, stems and leaves of Newbouldia laevis Thunb. screened by LC/ESI-Q-TOF-MS
(Elsevier, 2020) Osei-Safo, D.; Amewu, R.K.; Dermane, A.; et al.
Newbouldia laevis (P. Beauv.) Seem. or “Boundary Tree” is a medium sized angiosperm in the Bignoniaceae family. It is native to tropical Africa, especially used in West Africa to mark property boundaries in rural areas. Despite its intensive use in folk medicine, the plant chemical composition is under investigated. The study is aimed at identifying the chemical constituents of N. laevis crude plant extracts by high-performance liquid chromatography (HPLC) on line with an untargeted high-resolution mass spectrometry. The used HPLC method showed to be suitable for the determination of withasomnine, newbouldine, and lapachol derivatives together with other known bioactive compounds like phytosterols and triterpenoids. The importance of these chemical constituents is discussed with respect to the role of N. laevis in West African ethnomedicine. © 2020 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).
Synthetic and Naturally Occurring Heterocyclic Anticancer Compounds with Multiple Biological Targets
(MDPI, 2021) Osei-Safo, D.; Amewu, R.K.; Sakyi, P.O.; et al.
Abstract: Cancer is a complex group of diseases initiated by abnormal cell division with the potential of spreading to other parts of the body. The advancement in the discoveries of omics and bio- and cheminformatics has led to the identification of drugs inhibiting putative targets including vascular endothelial growth factor (VEGF) family receptors, fibroblast growth factors (FGF), platelet derived growth factors (PDGF), epidermal growth factor (EGF), thymidine phosphorylase (TP), and neuropeptide Y4 (NY4), amongst others. Drug resistance, systemic toxicity, and drug ineffectiveness for various cancer chemo-treatments are widespread. Due to this, efficient therapeutic agents targeting two or more of the putative targets in different cancer cells are proposed as cutting edge treatments. Heterocyclic compounds, both synthetic and natural products, have, however, contributed immensely to chemotherapeutics for treatments of various diseases, but little is known about such compounds and their multimodal anticancer properties. A compendium of heterocyclic synthetic and natural product multitarget anticancer compounds, their IC50, and biological targets of inhibition are therefore presented in this review.
Antischistosomal, antionchocercal and antitrypanosomal potentials of some Ghanaian traditional medicines and their constituents
(PLOS, 2020) Osei-Safo, D.; Twumasi, E.B.; Akazue, P.I.
Background Ghana is endemic for some neglected tropical diseases (NTDs) including schistosomiasis, onchocerciasis and lymphatic filariasis. The major intervention for these diseases is mass drug administration of a few repeatedly recycled drugs which is a cause for major concern due to reduced efficacy of the drugs and the emergence of drug resistance. Evidently, new treatments are needed urgently. Medicinal plants, on the other hand, have a reputable his- tory as important sources of potent therapeutic agents in the treatment of various diseases among African populations, Ghana inclusively, and provide very useful starting points for the discovery of much-needed new or alternative drugs. Methodology/Principal findings In this study, extracts of fifteen traditional medicines used for treating various NTDs in local communities were screened in vitro for efficacy against schistosomiasis, onchocerciasis and African trypanosomiasis. Two extracts, NTD-B4-DCM and NTD-B7-DCM, prepared from traditional medicines used to treat schistosomiasis, displayed the highest activity (IC50 = 30.5 μg/mL and 30.8 μg/mL, respectively) against Schistosoma mansoni adult worms. NTD-B2-DCM, also obtained from an antischistosomal remedy, was the most active against female and male adult Onchocera ochengi worms (IC50 = 76.2 μg/mL and 76.7 μg/mL, respectively). Antitrypanosomal assay of the extracts against Trypanosoma brucei brucei gave the most promising results (IC50 = 5.63 μg/mL to 18.71 μg/mL). Incidentally, NTD-B4- DCM and NTD-B2-DCM, also exhibited the greatest antitrypanosomal activities (IC50 = PLOS NEGLECTED TROPICAL DISEASES PLOS Neglected Tropical Diseases | https://doi.org/10.1371/journal.pntd.0008919 December 31, 2020 1 / 21 a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Twumasi EB, Akazue PI, Kyeremeh K, Gwira TM, Keiser J, Cho-Ngwa F, et al. (2020) Antischistosomal, antionchocercal and antitrypanosomal potentials of some Ghanaian traditional medicines and their constituents. PLoS Negl Trop Dis 14(12): e0008919. https://doi.org/ 10.1371/journal.pntd.0008919 Editor: Sabine Specht, University of Zurich, SWITZERLAND Received: April 20, 2020 Accepted: October 26, 2020 Published: December 31, 2020 Peer Review History: PLOS recognizes the benefits of transparency in the peer review process; therefore, we enable the publication of all of the content of peer review and author responses alongside final, published articles. The editorial history of this article is available here: https://doi.org/10.1371/journal.pntd.0008919 Copyright: © 2020 Twumasi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the manuscript and its Supporting Information files. 5.63 μg/mL and 7.12 μg/mL, respectively). Following the favourable outcome of the antitry- panosomal screening, this assay was selected for bioactivity-guided fractionation. NTD-B4- DCM, the most active extract, was fractionated and subsequent isolation of bioactive con- stituents led to an eupatoriochromene-rich oil (42.6%) which was 1.3-fold (IC50 <0.0977 μg/ mL) more active than the standard antitrypanosomal drug, diminazene aceturate (IC50 = 0.13 μg/mL). Conclusion/Significance These findings justify the use of traditional medicines and demonstrate their prospects towards NTDs drug discovery.
In vitro activities of crude extracts and triterpenoid constituents of Dichapetalum crassifolium Chodat against clinical isolates of Schistosoma haematobium
(Cellpress, 2020) Chama, M.A.; Onyame, H.A.; Fleischer, C.; et al.
Dichapetalum crassifolium Chodat (Dichapetalaceae) is widely distributed in Africa, Tropical Asia and Latin America. As part of our quest for potential bioactive lead compounds for various neglected tropical diseases, we report the anti-schistosomal potential of the crude extracts and chemical constituents of the stems and roots of Dichapetalum crassifolium. Column chromatography of extracts of the stems and roots led to the isolation and identification of three oleanane-type triterpenoids, friedelan-3β-ol (1), friedelan-3-one (2), and maslinic acid (3); the ursane-type tritepenoid, pomolic acid (4) and the dammarane-type tetracyclic triterpenoids, dichapetalin A (5) and dichapetalin M (6). Dichapetalin A was isolated from only the roots. Isolated compounds were identified by comparison of their physico-chemical and spectral data with published data. The highest in vitro antischistosomal activity (IC50) of the crude extracts against clinical isolates of Schistosoma haematobium (Bilharz 1852) was 248.6 μg/ml for the ethyl acetate extract of the root while dichapetalin A gave the highest activity at 151.1 μg/ml among the compounds compared with the 15.5 μg/ml for the standard drug, praziquantel. The rest of the compounds showed activities in the order 177.9, 191.0, and 378.1 μg/ml respectively for mixture of β-sitosterol/stigmasterol, dichapetalin M and friedelan-3-one. The least active extract was the methanol extract of the stem (893.7 μg/ml). The constituents of D. crassifolium showed activity against the S. haematobium that are below praziquantel. It is envisaged that the presence of multiple layers and the minute sizes of pores in the egg shells, may preclude penetration of eggs by the compounds
Evaluating the factors that influence public sector involvement in Ghanaian public-private partnership (PPP) power projects
(Journal of Facilities Management, 2023) Kukah, A.S.K.; Owusu-Manu, D-G.; Kukah, R.M.K.; et al.
Purpose – In comparison to other countries, power generation in Sub-Sahara Africa is poor. Public–private partnership (PPP) model has become increasingly popular for addressing infrastructural challenges, especially in the power sector. The purpose of this study is to evaluate and classify the factors that influence public sector involvement in Ghanaian PPP power projects. Design/methodology/approach – Using purposive and snowball sampling techniques, questionnaires were used to gather responses from experts in the PPP power sector in a two round Delphi survey. Analytical tools adopted were descriptive statistics, mean score ranking, Cronbach’s alpha and factor analysis. Findings – The most significant factors that influence public sector involvement in PPP power projects were: achieving improved value for money; access to additional capital; increased certainty of projects; greater efficiency of project delivery services; and improved ability to deliver new infrastructure. From factor analysis, the four components were: value for money and efficiency; capital and skills; innovation and technology; and project delivery
Inhibiting Leishmania donovani Sterol Methyltransferase to Identify Lead Compounds Using Molecular Modelling
(Pharmaceuticals, 2023) Sakyi, P.O.; Kwofie, S.K.; Tuekpe, J.K.; et al.
The recent outlook of leishmaniasis as a global public health concern coupled with the reportage of resistance and lack of efficacy of most antileishmanial drugs calls for a concerted effort to find new leads. The study combined In silico and in vitro approaches to identify novel potential synthetic small-molecule inhibitors targeting the Leishmania donovani sterol methyltransferase (LdSMT). The LdSMT enzyme in the ergosterol biosynthetic pathway is required for the parasite’s membrane fluidity, distribution of membrane proteins, and control of the cell cycle. The lack of LdSMT homologue in the human host and its conserved nature among all Leishmania parasites makes it a viable target for future antileishmanial drugs. Initially, six known inhibitors of LdSMT with IC50 < 10 µM were used to generate a pharmacophore model with a score of 0.9144 using LigandScout. The validated model was used to screen a synthetic library of 95,630 compounds obtained from InterBioScreen limited. Twenty compounds with pharmacophore fit scores above 50 were docked against the modelled three-dimensional structure of LdSMT using AutoDock Vina. Consequently, nine compounds with binding energies ranging from −7.5 to −8.7 kcal/mol were identified as potential hit molecules. Three compounds comprising STOCK6S-06707, STOCK6S-84928, and STOCK6S-65920 with respective binding energies of −8.7, −8.2, and −8.0 kcal/mol, lower than 22,26-azasterol (−7.6 kcal/mol), a known LdSMT inhibitor, were selected as plausible lead molecules. Molecular dynamics simulation studies and molecular mechanics Poisson–Boltzmann surface area calculations showed that the residues Asp25 and Trp208 were critical for ligand binding. The compounds were also predicted to have antileishmanial activity with reasonable pharmacological and toxicity profiles. When the antileishmanial activity of the three hits was evaluated in vitro against the promastigotes of L. donovani, mean half-maximal inhibitory concentrations (IC50) of 21.9 ± 1.5 µM (STOCK6S-06707), 23.5 ± 1.1 µM (STOCK6S-84928), and 118.3 ± 5.8 µM (STOCK6S-65920) were obtained. Furthermore, STOCK6S-84928 and STOCK6S-65920 inhibited the growth of Trypanosoma brucei, with IC50 of 14.3 ± 2.0 µM and 18.1 ± 1.4 µM, respectively. The identified compounds could be optimised to develop potent antileishmanial therapeutic agents.
Docking and Molecular Dynamics Identify Leads against 5 Alpha Reductase 2 for Benign Prostate Hyperplasia Treatment
(Journal of Chemistry, 2023) Saah, S.A.; Sakyi, P.O.; Ayittey, K.; et al.
Steroid 5 alpha-reductase 2 (5αR-2) is a membrane-embedded protein that together with other isoforms plays a key role in the metabolism of steroids. Tis enzyme catalyzes the reduction of testosterone to the more potent ligand, dihydrotestosterone (DHT) in the prostate. Androgens, testosterone, and DHT play important roles in prostate growth, development, and function. At the same time, both testosterone and DHT have been implicated in the pathogenesis of benign prostate hyperplasia (BPH). Inhibition of the DHTformation, therefore, provides a therapeutic strategy that ofers the possibility of preventing, delaying, or treating BPH. Currently, two steroidal drugs that inhibit 5αR-2, dutasteride and fnasteride, have been approved for clinical use. Tese two come at a high cost and also portray undesirable sexual side efects which necessitate the need to fnd new chemotherapeutic alternatives for the disease. Based on the aforementioned, fnasteride and dutasteride were subjected to scafold hopping, fragment-based de novo design, molecular docking, and molecular dynamics simulations employing databases like ChEMBL, DrugBank, PubChem, ChemSpider, and Zinc15 in the identifcation of potential hits targeting 5αR-2. Altogether, ten novel compounds targeting 5αR-2 were identifed with binding energies lower or comparable to fnasteride and dutasteride, the main inhibitors for this target. Molecular docking and molecular dynamics simulations studies identify amino acid residues Glu57, Phe219, Phe223, and Leu224 to be critical for ligand binding and complex stability. Te physicochemical and pharmacological profling suggests the potential of the hit compounds to be drug-like and orally active. Similarly, the quality parameter assessments revealed the hits possess LELP greater than 3 implying their promise as lead-like molecules. Te compounds A5, A9, and A10 were, respectively, predicted to treat prostate disorders with Pa (0.188, 0.361, and 0.270) and Pi (0.176, 0.050, and 0.093), while A8 and A9 were found to be associated with BPH treatment with Pa (0.09 and 0.127) and Pi (0.077 and 0.033), respectively. Structural similarity searches via DrugBank identifed the drugs faropenem, acemetacin, estradiol valerate, and yohimbine to be useful for BPH treatment suggesting the de novo designed ligands as potential chemotherapeutic agents for treating this disease.
Theoretical studies on the reaction mechanisms of the oxidation of tetramethylethylene using MO3Cl (M=Mn, Tc and Re)
(Journal of Molecular Graphics and Modelling, 2023) Fosu, E.A.; Obuah, C.; Hamenu, L.; Aniagyei, A.; Oppong, A.; Ainooson, M.K.; Muller, A.
A theoretical study on the reaction mechanisms of the addition of transition metal oxo complexes of the type MO3Cl (M = Mn, Tc, and Re) to tetramethylethylene (TME) is presented. Theoretical calculations using B3LYP/ LACVP* and M06/LACVP* (LACVP* is a combination of the 6-31G(d) basis set along with LANL2DZ pseudo potentials on the metallic centres) were performed and the results are discussed within the framework of reaction energetics. The nature of the stability of the reaction mechanisms was equivalent for both theories. However, the M06/LACVP* simulations generally had slightly lower energies and shorter bond lengths compared to the B3LYP/LACVP* computations. Furthermore, it was observed that the reaction does not proceed via the stepwise reaction mechanism due to kinetic and thermodynamic instabilities. Epoxidation was also found to occur via the [2 + 2] concerted reaction mechanism for the MO3Cl (M = Tc and Re) whereas the permanganyl chloride complex epoxidizes TME via the [2 + 1] concerted reaction mechanism on the singlet potential energy surface (PES). Dioxylation was observed to proceed via the [3 + 2] route for the addition of MO3Cl (M = Tc and Re) and TME. Results indicate that all reaction surfaces were unselective except for the permanganyl chloride catalyzed surface which leads to the formation of epoxides exclusively. Changes in temperatures from 298.15 K to 373.15 K, resulted in kinetically and thermodynamically unstable reaction pathways as the activation and reaction energies increased generally. On the singlet PES, the rate constant calculations showed that the [3 + 2] catalyzed surface reaction mechanism leading to dioxylation was faster than the [2 + 2] mechanism in cases where plausible. Theoretical values from the global reactivity parameters, namely the chemical hardness, chemical potential, electrophilic and nucleophilic indices, are in good correlation with the DFT activation and reaction energies at both levels of theories. Thus, as the electrophilic nature of the metal decreases from Mn to Re, so do the activation and reaction energies increase from Mn to Re, indicating that the higher the electrophilicity of the metal centre, the more spontaneous the oxidation reaction.
A new sulfonamide-based chemosensor for potential fluorescent detection of Cu2þ and Zn2þ ions
(Tetrahedron, 2023) Amoah, C.; Obuah, C.; Ainooson, M.K.; Oppong, A.; Muller, A.
In recent times, there has been an increased demand in the search for probing materials for numerous substances in the environment such as the detection of metals ions. In this study, a new class of pyrazolyl-sulfonamide derivatives of para-nitroaniline were synthesized following a multistep approach. The ligands and complexes were characterized using NMR spectroscopy, IR spectroscopy, and mass spectrometry. All the compounds C1eC3 were synthesized in very good yields (85%e92%) and their photo-physical properties measured. All the compounds show fluorescence behaviour with emissions within the UV and far visible range with quantum yields between 7.7% and 25.7%. TD-DFT calculations predictions for the electronic transitions present are in good agreement with experimental observations. Fluorescent probing studies conducted on the compounds show that C1eC3 were analytically sensitive and possessed significant selectivity towards Cu2þ (for C3) and Zn2þ (for C1 and C2) ions with detection limits between 0.011 and 0.103 mg/L for Cu2þ ions and 0.002e0.135 mg/L for Zn2þ ions. Overall, C1 was found to be the most sensitive molecule for the metals studied, having good quantum yield and better selectivity for Zn2þ ion compared to Cu2þ.
Evaluation of the fluorescent-thin layer chromatography (f-TLC) for the diagnosis of Buruli ulcer disease in Ghana
(PLOS ONE, 2022) Amewu, R.K; Akolgo, G.A; Asare, M.E; Abdulai, Z; Ablordey, A.S; Asiedu, K
Abstract Background Buruli ulcer is a tissue necrosis infection caused by an environmental mycobacterium called Mycobacterium ulcerans (MU). The disease is most prevalent in rural areas with the highest rates in West and Central African countries. The bacterium produces a toxin called mycolactone which can lead to the destruction of the skin, resulting in incapacitating deformities with an enormous economic and social burden on patients and their caregivers. Even though there is an effective antibiotic treatment for BU, the control and management rely on early case detection and rapid diagnosis to avert morbidities. The diagnosis of Mycobacterium ulcerans relies on smear microscopy, culture histopathology, and PCR. Unfortunately, all the current laboratory diagnostics have various limitations and are not available in endemic communities. Consequently, there is a need for a rapid diagnostic tool for use at the community health centre level to enable diagnosis and confirmation of suspected cases for early treatment. The present study corroborated the diagnostic performance and utility of fluorescent- thin layer chromatography (f-TLC) for the diagnosis of Buruli ulcer. Methodology/Principal findings The f-TLC method was evaluated for the diagnosis of Buruli ulcer in larger clinical samples than previously reported in an earlier preliminary study Wadagni et al. (2015). A total of 449 patients suspected of BU were included in the final data analysis out of which 122 (27.2%) were positive by f-TLC and 128 (28.5%) by PCR. Using a composite reference method generated from the two diagnostic methods, 85 (18.9%) patients were found to be truly infected with M. ulcerans, 284 (63.3%) were uninfected, while 80 (17.8%) were misidentified as infected or noninfected by the two methods. The data obtained was used to determine the discriminatory accuracy of the f-TLC against the gold standard IS2404 PCR through the analysis of its sensitivity, specificity, positive (+LR), and negative (–LR) likelihood ratio. The positive (PPV) and negative (NPV) predictive values, area under the receiver operating characteristic curve Azevedo et al. (2014), and diagnostic odds ratio were used to assessthe predictive accuracy of the f-TLC method. The sensitivity of f-TLC was 66.4% (85/128), specificity was 88.5% (284/321), while the diagnostic accuracy was 82.2% (369/449). The AUC stood at 0.774 while the PPV, NPV, +LR, and–LR were 69.7% (85/122), 86.9% (284/ 327), 5.76, and 0.38, respectively. The use of the rule-of-thumb interpretation of diagnostic tests suggests that the method is good for use as a diagnostic tool. Conclusions/Significance Larger clinical samples than previously reported had been used to evaluate the f-TLC method for the diagnosis of Buruli ulcer. A sensitivity of 66.4%, a specificity of 88.5%, and diagnostic accuracy of 82.2% were obtained. The method is good for diagnosis and will help in making early clinical decisions about the patients as well as patient management and facilitating treatment decisions. However, it requires a slight modification to address the challenge of background interference and lack of automatic readout to become an excellent diagnostic tool. Introduction

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