Objective: Falciparum malaria is a major global health concern, affecting more than half of the world's population and causing over half a million deaths annually. Red cell invasion is a crucial step in the parasite's life cycle, where the parasite invade human erythrocytes to sustain infection and ensure survival. Two parasite proteins, Apical Membrane Antigen 1 (AMA-1) and Rhoptry Neck Protein 2 (RON2), are involved in tight junction formation, which is an essential step in parasite invasion of the red blood cell. Targeting the AMA-1 and RON2 interaction with inhibitors halts the formation of the tight junction, thereby preventing parasite invasion, which is detrimental to parasite survival. This study leverages machine learning (ML) to predict potential small molecule inhibitors of the AMA-1-RON2 interaction, providing putative antimalaria compounds for further chemotherapeutic exploration. Method: Data was retrieved from the PubChem database (AID 720542), comprising 364,447 inhibitors and non-inhibitors of the AMA-1-RON2 interaction. The data was processed by computing Morgan fingerprints and divided into training and testing with an 80:20 ratio, and the classes in the training data were balanced using the Synthetic Minority Oversampling Technique. Five ML models developed comprised Random Forest (RF), Gradient Boost Machines (GBMs), CatBoost (CB), AdaBoost (AB) and Support Vector Machine (SVM). The performances of the models were evaluated using accuracy, F1 score, and receiver operating characteristic-area under the curve (ROC-AUC) and validated using held-out data and a y-randomization test. An applicability domain analysis was carried out using the Tanimoto distance with a threshold set at 0.04 to ascertain the sample space where the models predict with confidence. Results: The GBMs model emerged as the best, achieving 89% accuracy and a ROC-AUC of 92%. CB and RF had accuracies of 88% and 87%, and ROC-AUC scores of 93% and 91%, respectively. Conclusions: Experimentally validated inhibitors of the AMA-1-RON2 interaction could serve as starting blocks for the next-generation antimalarial drugs. The models were deployed as a web-based application, known as PLASMOpred.

Malaria, caused by Plasmodium parasites, remains life-threatening, with Plasmodium falciparum responsible for severe cases. The parasite's invasion of Red Blood Cells (RBCs) is critical for infection. The interaction between Reticulocyte Binding Protein Homologue 5 (RH5), Basigin, monoclonal antibodies and Cysteine-Rich Protective Antigen (CyRPA) with glycan on RBCs is essential for this process. This study aims to identify small molecules inhibiting the RH5-CyRPA-RIPr invasion complex. A library of 2299 compounds from FDA-approved drugs and African natural products in the ZINC database was screened using molecular docking. Binding sites for Basigin, monoclonal antibodies and glycans on RH5 and CyRPA were targeted, with binding affinity cutoffs of -8.5 kcal/mol for monoclonal antibodies and -7.0 kcal/mol for CyRPA and Basigin. Compounds were assessed for pharmacokinetics, solubility, drug-likeness, lead-likeness and biological activity using the PASS online server. Molecular dynamics simulations and free energy calculations evaluated stability and binding efficiency. Nine hits for RH5 and three for CyRPA showed favorable stability and anti-protozoal activity (up to 0.65). African natural products exhibited similarities with drugs like Nequinate and Cyanidin, supporting further research. Promising small molecules were identified as potential inhibitors of P. falciparum invasion, laying a foundation for experimental validation and drug development.

The current therapeutic agents for the treatments of visceral leishmaniasis are ineffective, and cytotoxic. Therefore, there is the urgent need for new chemotypes for the treatment of the disease with novel mechanisms of action. In our previous investigation, we identified the triazolopyridazine, STOCK6S-84928 as a potential inhibitor of Leishmania donovani sterol methyltransferase (LdSMT) with IC50 value of 118.3 µM. To improve the biological activity of the initial hit compound, we hereby describe the results of structural-activity relationship studies on STOCK6S-84928 via chemical modifications on the scaffold and virtually screening of 250 compounds obtained against the Modeller generated LdSMT structure. A total of 21 compounds were found to have binding energies ranging from − 7.0 to − 9.2 kcal/mol lower or comparable to the 22,26-azasterol (− 7.6 kcal/mol), the known inhibitor of the target. Molecular docking and molecular dynamics simulations revealed Ile272 and Tyr275 to be pivotal for ligand binding. The compounds were predicted to possess leishmanicidal activities with good drug-like properties. Significantly, the compounds 8, 9, 21, and 23 were predicted to possess antineoplastic, anti-inflammatory, analgesics, protein and MAP kinase inhibitory activities with probability of activity (Pa) > 0.2 and probability of inactivity (Pi) < 0.16. Through the applications of cyclization, amination, Williamson’s ether synthesis, and Suzuki cross-coupling reactions, the selected analogues of STOCK6S-84928 were synthesised in moderate to high yields and characterized by FTIR, LC–MS, and NMR spectroscopy methods. In vitro antileishmanial evaluation of the synthesized compounds identified 23 as the most potent, exhibiting L. donovani promastigotes inhibitory activities with IC50 value of (1.9 ± 0.1) µM. The ortho-difluoropheneyl group as well as the triazolopyridine moieties were suspected to be responsible for the observed activity. Similarly, the compounds 10 and 16 required (0.8 ± 0.1) µM and (0.6 ± 0.0) µM, respectively to eliminate 50

Background/Objectives: Pteridine reductase 1 (PTR1) has been one of the prime targets for discovering novel antileishmanial therapeutics in the fight against Leishmaniasis. This enzyme catalyzes the NADPH-dependent reduction of pterins to their tetrahydro forms. While chemotherapy remains the primary treatment, its effectiveness is constrained by drug resistance, unfavorable side effects, and substantial associated costs. Methods: This study addresses the urgent need for novel, cost-effective drugs by employing in silico techniques to identify potential lead compounds targeting the PTR1 enzyme. A library of 1463 natural compounds from AfroDb and NANPDB, prefiltered based on Lipinski’s rules, was used to screen against the LmPTR1 target. The X-ray structure of LmPTR1 complexed with NADP and dihydrobiopterin (Protein Data Bank ID: 1E92) was identified to contain the critical residues Arg17, Leu18, Ser111, Phe113, Pro224, Gly225, Ser227, Leu229, and Val230 including the triad of residues Asp181-Tyr194-Lys198, which are critical for the catalytic process involving the reduction of dihydrofolate to tetrahydrofolate. Results: The docking yielded 155 compounds meeting the stringent criteria of −8.9 kcal/mol instead of the widely used −7.0 kcal/mol. These compounds demonstrated binding affinities comparable to the known inhibitors; methotrexate (−9.5 kcal/mol), jatrorrhizine (−9.0 kcal/mol), pyrimethamine (−7.3 kcal/mol), hardwickiic acid (−8.1 kcal/mol), and columbamine (−8.6 kcal/mol). Protein–ligand interactions and molecular dynamics (MD) simulation revealed favorable hydrophobic and hydrogen bonding with critical residues, such as Lys198, Arg17, Ser111, Tyr194, Asp181, and Gly225. Crucial to the drug development, the compounds were physiochemically and pharmacologically profiled, narrowing the selection to eight compounds, excluding those with potential toxicities. The five selected compounds ZINC000095486253, ZINC000095486221, ZINC000095486249, 8alpha-hydroxy-13-epi-pimar-16-en-6,18-olide, and pachycladin D were predicted to be antiprotozoal (Leishmania) with Pa values of 0.642, 0.297, 0.543, 0.431, and 0.350, respectively. Conclusions: This study identified five lead compounds that showed substantial binding affinity against LmPTR1 as well as critical residue interactions. A 100 ns MD combined with molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations confirmed the robust binding interactions and provided insights into the dynamics and stability of the protein–ligand complexes.

Groundwater is vital for drinking, agriculture, and domestic use in Sokoban Wood Village, Ghana, but concerns exist about its quality. This study assessed the suitability of 20 groundwater samples for domestic purposes. The study was carried out in 2023. We collected samples from boreholes and hand-dug wells using standard methods, analyzing them for various physicochemical parameters (pH, electrical conductivity, turbidity, nitrates, fluorides, and heavy metals). The microbiological analysis assessed fecal coliforms and E. Coli to identify microbial contamination. Established methodologies were used to evaluate potential health risks (carcinogenic and non-carcinogenic) associated with heavy metals. The Water Quality Index (WQI), Hazard Potential Index (HPI), and Heavy Metal Evaluation Index (HEI) provided a comprehensive water quality evaluation. The results revealed that the water fell below the recommended WHO pH range for drinking water. While most other parameters and heavy metals fell within WHO guidelines, 25% of the samples contained fecal coliforms and E. Coli, indicating ongoing microbial contamination. The overall cancer risk was low for all age groups. Although some parameters met WHO standards, the WQI classified 20% of the samples as not of good quality. Despite this, the HPI and HEI (-4.62 and 0.001) suggested generally good water quality based on heavy metal content. In conclusion, despite some positive indicators, acidic water and microbial contamination raise concerns. Regular monitoring and potential treatment measures are crucial to ensure safe drinking water for the Sokoban Wood Village community.

Cervical cancer is the fourth most diagnosed cancer and the fourth leading cause of cancer death in women globally. Its onset and progression have been attributed to high-risk human papillomavirus (HPV) types, especially 16 and 18, while the Epstein–Barr virus (EBV) is believed to also significantly contribute to cervical cancer growth. The E6 protein associated with high-risk HPV strains, such as HPV16 and HPV18, is known for its role in promoting cervical cancer and other anogenital cancers. E6 proteins contribute to the malignant transformation of infected cells by targeting and degrading tumor suppressor proteins, especially p53. On the other hand, EBV nuclear antigen 1 (EBNA1) plays a crucial role in the maintenance and replication of the EBV genome in infected cells. EBNA1 is believed to increase HPV E6 and E7 levels, as well as c-MYC, and BIRC5 cellular genes in the HeLa cell line, implying that HPV/EBV co-infection accelerates cervical cancer onset and growth. Thus, the E6 and EBNA1 antigens of HPV and EBV, respectively, are attractive targets for cervical cancer immunotherapy. This study, therefore, virtually screened for potential drug candidates with good binding affinity to all three oncoviral proteins, HPV16 E6, HPV18 E6, and EBNA1. The compounds were further subjected to ADMET profiling, biological activity predictions, molecular dynamics (MD) simulations, and molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) calculations. A total of six compounds comprising ZINC000013380012, ZINC000070454124, ZINC000014588133, ZINC000085568136, ZINC000095909247, and ZINC000085597263 demonstrated very strong affinity (≤−60 kJ/mol) to the three oncoviral proteins (EBNA1, HPV16 E6, and HPV18 E6) after being subjected to docking, MD, and MM/PBSA. These compounds demonstrated relatively stronger binding than the controls used, inhibitors of EBNA1 (VK-1727) and HPV E6 (baicalein and gossypetin). Biological activity predictions also corroborated their antineoplastic, p53-enhancing, Pin1 inhibitory, and JAK2 inhibitory activities. Further experimental testing is required to validate the ability of the shortlisted compounds to silence the insidious effects of HPV E6 and EBNA1 proteins in cervical cancers.

Approximately 60% of men globally over the age of 50 experience a diminished quality of life as a result of benign prostatic hyperplasia (BPH). Consequently, while the national direct cost for managing BPH is hovering around $4 billion in the USA, the individual direct cost for medications is estimated at $1536 and $425 annually for the USA and Ghana, respectively. Due to the chemotherapeutic drawbacks in BPH treatment, a concerted effort is urgently needed to find new chemotypes with novel mechanism of action to combat the disease. This research aims to employ computational techniques to identify new compounds from ethno-pharmacological plants from Ghana for treating BPH. Altogether, 250 natural products from Croton membranaceus, Heliotropium angiospermum, Annona muricata, Serenoa repens, Cissus quadrangularis, Tribulus terrestrials, Vernonia amagdalina and Momordica foetida from Ghanaian origin were virtually screened against 5alpha reductase 2 (5aR2), a primary drug target implicated in the parthenogenesis of BPH. Out of the 254 compounds docked, three compounds (A, B and C) showed a binding energy lower than testosterone (-10.4 kcal/mol), the main substrate of the target and comparative to finasteride (-11.7 kcal/mol), one of the drugs currently used for treating the disease. Molecular docking and dynamics simulations studies revealed Leu224 to be critical for ligand binding and complex stability. The pharmacological and physicochemical profiles show the compounds to possess good pharmacodynamics with negligible toxicities. While the compounds A, C, G, H, I and J were, respectively, predicted to treat prostate disorders with Pa (0.909, 0.221, 0.743, 0.729, 0.978, and 0.443) and Pi (0.003, 0.132, 0.005,0.005, 0.002, 0.016), that of A, B, D, G, H, I, and J were found to be associated with the inhibition of 5alpha reductase with Pa (0.840, 0.102, 0.097, 0.377, 0.123, 0.909, and 0.201) and Pi (0.001, 0.075, 0.089, 0.003, 0.036, 0.001, and 0.004) respectively. These lead-like compounds possessing plausible chemotherapeutic moieties with putative 5aR2 inhibitory potential need further experimental validation via in vitro studies.

In exploring the potential of agricultural waste as an efficient adsorbent, acid-activated coconut husk biochar was prepared, characterized and applied to remove amoxicillin from wastewater. The mechanism of adsorption was also investigated through isotherm and kinetic studies. The biochar was activated with HNO3 for 2 h at 25 degrees C and investigated under varying experimental conditions of pH (1-11), initial amoxicillin concentration (0.5-2.5 mg/L), adsorbent dosage (2-20 mg) and contact time (0-24 h). The adsorption process was characterized by rapid attainment of adsorption equilibrium and high values of adsorption capacity. Acid activation had a significant impact on the adsorptive capacity of biochar as removal efficiency improved from 90% (over an hour) to 98.9% (within 40 min). The FTIR results confirmed the characteristic adsorption peaks of C-H, =C-H, C=C, C-O, C=O and O-H, suggesting the dominant presence of aromatic and carbonyl functional groups on the surface of the biochar. Adjustments in peak shapes and transmittance were observed for these functional groups after the adsorption; highlighting the likely interaction between the biochar and the amoxicillin during the adsorption which has been succinctly proposed. The SEM micrographs showed the growth of leaf-like flakes of irregular shapes and pores essential for the adsorption. The rate and mechanism of adsorption were driven by the variable surface charge of the adsorbent and the degree of ionization of the adsorbates, which were largely controlled by the solution pH. Adsorption rates were highest in the acidic medium, peaking around a pH of 3, then remained relatively stable between pHs of 5 and 7 before reducing dramatically with increasing pH in the alkaline region. The adsorption best followed the Langmuir model of isotherm while the kinetics mimicked the pseudo-second order (PSO). The findings suggest that HNO3-activated coconut biochar is a promising, low-cost and porous adsorbent effective for amoxicillin removal.

This study explores the synthesis of nanoparticles through the thermal decomposition of single-source precursors, a method gaining popularity due to its low cost, minimal environmental toxicity, rapidity, scalability, and the ability to form nanoparticles with few defects. Zinc ethyl carbamate was synthesized and characterized using 1H NMR and infrared spectroscopy. Its purity was confirmed through microelemental analysis and melting point determination. The melting point of the complex was determined to be 165 °C. The thermogravimetric analyses indicated a one-step decomposition of zinc ethyl carbamate with a decomposition onset of of 200 °C, yielding a stable ZnS residue. Further thermal decomposition led to the formation of wurtzite phase ZnS nanoparticles, as evidenced by XRD. SEM micrographs displayed mixed spherical, and cubic unevenly sized, polydispersed nanoparticles, while EDX revealed approximately a 1 : 1 Zn to S ratio. Estimated band gap from the Tauc's plot gave 3.93 eV and 3.42 eV for the nanoparticles synthesized at 300 and 400 °C respectively. The wide difference in the band gaps may be as a result of the larger particles observed at 400 °C and the deformations in the sample as observed in the SEM.

The study investigates the concentration of heavy metals in various lipsticks sold in Ghana and assesses the potential health risks associated with their use. A total of 12 lipstick samples were analyzed using an X-ray fluorescence (XRF) analyzer for metals, including chromium (Cr), manganese (Mn), nickel (Ni), copper (Cu), cadmium (Cd), and lead (Pb). The findings revealed that Cr levels ranged from below detection limits to 2554.20 mg/kg, with five samples significantly exceeding the acceptable 1 mg/kg limit set by Health Canada. Mn concentrations varied from 0.09 mg/kg to 823.00 mg/kg, and Ni levels were detected up to 228.40 mg/kg, indicating potential risks of neurotoxicity and contact dermatitis. Cu was found in extremely high concentrations, particularly in samples S1 (14053.33 mg/kg) and S7 (1939.84 mg/kg), exceeding the acceptable 100 mg/kg limit, suggesting severe contamination and potential systemic toxicity. Cd concentrations in most samples surpassed the FDA limit of 3 mg/kg, posing risks of kidney damage. In comparison, Pb concentrations in several samples approached or exceeded the FDA limit of 10 mg/kg, indicating potential neurotoxic effects. Health risk assessments for dermal and oral exposure were conducted, with hazard quotients for non-carcinogenic risks remaining below 1, suggesting minimal immediate health risks. However, the relative intake indices (RII) for Cr, Cd, and Pb in oral risk assessments indicated significant exposure levels far exceeding acceptable daily intakes (ADI) for heavy users. These findings highlight the need for stricter regulation and consumer awareness of the potential dangers posed by heavy metals in cosmetics. Enhanced safety standards and regular monitoring are imperative to protect public health from the adverse effects of toxic metals in beauty products.

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.

The mortalities and morbidities of leishmaniasis are high and the disease is under reported globally. The absence of vaccines coupled with chemotherapeutic challenges including chemoresistance, scarcity and toxicity have made the fight against leishmaniasis an arduous one. Furthermore, the treatment options currently available for leishmaniasis are long and sometimes require hospitalization. There is therefore the need to explore novel pathways to identify new compounds with alternative mechanisms of action. A pharmacophore-based screening was employed in identifying new potential inhibitors with unique scaffolds targeting Leishmania donovani sterol methyltransferase (LdSMT), a key enzyme for ergosterol biosynthesis. To accomplish this, 22,26-azasterol, a known inhibitor of this target and five other derivatives with IC50 less than 10 μM were used to generate a robust 3D pharmacophore model via LigandScout with a score of 0.9144. The validated model was used as a query to screen a library of 69034 natural products obtained from the InterBioScreen Limited. Compounds with pharmacophore fit scores above 50 were docked against the modelled structure of LdSMT. Altogether, ten molecules with binding energies between −7 and −11 kcal/mol were identified as potential bioactive molecules. The molecular dynamics simulation and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations reinforced the results from the docking studies suggesting the selected hits bind effectively at the active sites of the target protein. The compounds were observed to bind in the S-adenosine-L-homocysteine binding pocket of the modelled LdSMT with Trp208 and Val330 predicted as key residues critical for ligand binding. Prediction of biological activity with probability of activity (Pa) greater than probability of inactivity (Pi) revealed that seven compounds (STOCKIN-54848, STOCKIN-89115, STOCKIN-68720, STOCKIN-44724, STOCKIN-76694, STOCKIN-47277 and STOCKIN-95708) possessed antileishmanial properties. STOCKIN-89115, STOCKIN-68720, STOCKIN-44724, and STOCKIN-47277 were predicted to be membrane permeability inhibitors, while all ten hit compounds possessed antineoplastic activity. The compounds have the propensity of disrupting ergosterol biosynthesis leading to the suppression of growth in Leishmania donovani. The compounds were predicted to have good absorption, distribution, metabolism, excretion and toxicity profiles, hence their potential antileishmanial activity can be exploited upon experimental corroboration.

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.

Altered RNA editing has been linked to several neurodevelopmental disorders, including autism spectrum disorder (ASD) and intellectual disability, in addition to depression, schizophrenia, some cancers, viral infections and autoimmune disorders. The human ADAR2 is a potential therapeutic target for managing these various disorders due to its crucial role in adenosine to inosine editing. This study applied consensus scoring to rank potential ADAR2 inhibitors after performing molecular docking with AutoDock Vina and Glide (Maestro), using a library of 35,161 compounds obtained from traditional Chinese medicine. A total of 47 compounds were predicted to be good binders of the human ADAR2 and had insignificant toxicity concerns. Molecular dynamics (MD) simulations, including the molecular mechanics Poisson–Boltzmann surface area (MM/PBSA) procedure, also emphasized the binding of the shortlisted compounds. The potential compounds had plausible binding free energies ranging from −81.304 to −1068.26 kJ/mol from the MM/PBSA calculations. ZINC000085511995, a naphthoquinone had more negative binding free energy (−1068.26 kJ/mol) than inositol hexakisphosphate (IHP) [−873.873 kJ/mol], an agonist and a strong binder of ADAR2. The potential displacement of IHP by ZINC000085511995 in the IHP binding site of ADAR2 could be explored for possible deactivation of ADAR2. Bayesian-based biological activity prediction corroborates the neuropharmacological, antineoplastic and antiviral activity of the potential lead compounds. All the potential lead compounds, except ZINC000014612330 and ZINC000013462928, were predicted to be inhibitors of various deaminases. The potential lead compounds also had probability of activity (Pa) > 0.442 and probability of inactivity (Pi) < 0.116 values for treating acute neurologic disorders, except for ZINC000085996580 and ZINC000013462928. Pursuing these compounds for their anti-ADAR2 activities holds a promising future, especially against neurological disorders, some cancers and viral infections caused by RNA viruses. Molecular interaction, hydrogen bond and per-residue decomposition analyses predicted Arg400, Arg401, Lys519, Trp687, Glu689, and Lys690 as hot-spot residues in the ADAR2 IHP binding site. Most of the top compounds were observed to have naphthoquinone, indole, furanocoumarin or benzofuran moieties. Serotonin and tryptophan, which are beneficial in digestive regulation, improving sleep cycle and mood, are indole derivatives. These chemical series may have the potential to treat neurological disorders, prion diseases, some cancers, specific viral infections, metabolic disorders and eating disorders through the disruption of ADAR2 pathways. A total of nine potential lead compounds were shortlisted as plausible modulators of ADAR2.

Mortalities associated with leishmaniasis are skyrocketing at an alarming rate. Lack of vaccine for leishmaniasis treatment is making the fight against the disease an arduous one. Interestingly, apart from the expensive nature of leishmaniasis treatments, the mono- and combinational chemotherapeutic agents suffer drawbacks such as resistance, synergism resistance, systemic toxicity, and ineffectiveness. Due to this, the new paradigm proposed for combating this canker is an efficient therapeutic antileishmanial agent with multitarget inhibitory properties. Though natural products and their derivatives have long been known for their medicinal properties for treating various ailments, little is known for their multimodality antileishmanial effects. A plethora of structurally diverse natural products, their IC50, and their biological targets of inhibition are, therefore, discussed in this book chapter. Structural modifications of these natural products based on pharmacophoric analysis leading to the semi-synthesis of their derivatives are also presented. Additionally, a view on metallodrugs using these versatile natural products and their derivatives coordinated to transition metals geared toward leishmaniasis treatment is proposed.

This study assessed the physicochemical and microbiological quality of sachet drinking water samples in Kumasi, a major city in Ghana. Samples were collected from various sources within the city. Physicochemical properties, including pH, total dissolved solids, and concentrations of calcium, sodium, potassium, and magnesium ions, were analyzed following established protocols. Additionally, fluoride concentration was determined. The assessment criteria for water quality were based on the World Health Organization’s and the Ghana Standards Authority’s recommended standards for drinking water. The samples were also subjected to microbial analysis to detect the presence of E. coli and coliforms, and to evaluate microbial quality. The findings indicated that most physicochemical properties of the samples met the World Health Organization’s standards for safe drinking water, except for the slightly acidic pH. Total dissolved solids and the concentrations of calcium, sodium, potassium, fluoride and magnesium ions were within acceptable ranges. Strong positive correlations were observed among various physicochemical parameters of sachet water. However, microbial analysis revealed that 67% of the samples were contaminated with pathogenic microorganisms, including E. coli and coliforms, indicating poor microbiological quality. While sachet water samples generally meet physicochemical safety standards, addressing microbial quality is essential to ensure the safety of drinking water in Kumasi.

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. This 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 DHT formation, therefore, provides a therapeutic strategy that offers the possibility of preventing, delaying, or treating BPH. Currently, two steroidal drugs that inhibit 5αR-2, dutasteride and finasteride, have been approved for clinical use. These two come at a high cost and also portray undesirable sexual side effects which necessitate the need to find new chemotherapeutic alternatives for the disease. Based on the aforementioned, finasteride and dutasteride were subjected to scaffold hopping, fragment-based de novo design, molecular docking, and molecular dynamics simulations employing databases like ChEMBL, DrugBank, PubChem, ChemSpider, and Zinc15 in the identification of potential hits targeting 5αR-2. Altogether, ten novel compounds targeting 5αR-2 were identified with binding energies lower or comparable to finasteride 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. The physicochemical and pharmacological profiling 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. The 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 identified 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.

The therapeutic challenges pertaining to leishmaniasis due to reported chemoresistance and toxicity necessitate the need to explore novel pathways to identify plausible inhibitory molecules. Leishmania donovani 24-sterol methyltransferase (LdSMT) is vital for the synthesis of ergosterols, the main constituents of Leishmania cellular membranes. So far, mammals have not been shown to possess SMT or ergosterols, making the pathway a prime candidate for drug discovery. The structural model of LdSMT was elucidated using homology modeling to identify potential novel 24-SMT inhibitors via virtual screening, scaffold hopping, and de-novo fragment-based design. Altogether, six potential novel inhibitors were identified with binding energies ranging from −7.0 to −8.4 kcal/mol with e-LEA3D using 22,26-azasterol and S1–S4 obtained from scaffold hopping via the ChEMBL, DrugBank, PubChem, ChemSpider, and ZINC15 databases. These ligands showed comparable binding energy to 22,26-azasterol (−7.6 kcal/mol), the main inhibitor of LdSMT. Moreover, all the compounds had plausible ligand efficiency-dependent lipophilicity (LELP) scores above 3. The binding mechanism identified Tyr92 to be critical for binding, and this was corroborated via molecular dynamics simulations and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) calculations. The ligand A1 was predicted to possess antileishmanial properties with a probability of activity (Pa) of 0.362 and a probability of inactivity (Pi) of 0.066, while A5 and A6 possessed dermatological properties with Pa values of 0.205 and 0.249 and Pi values of 0.162 and 0.120, respectively. Structural similarity search via DrugBank identified vabicaserin, daledalin, zanapezil, imipramine, and cefradine with antileishmanial properties suggesting that the de-novo compounds could be explored as potential antileishmanial agents.

The study aimed to ascertain the levels of trace elements present in the face powders marketed in Ghana. Fifteen different brands of facial makeup powders were purchased from a local market in Ghana. The samples were analyzed using an X-ray fluorescence (XRF) analyzer to determine the concentrations of 16 elements (Pb, As, Hg, Zn, Fe, Mn, Cr, Ti, Cu, Ni, Co, Sb, Cd, Ag, Sn, and Au). The contents of the trace elements were ordered in the following descending order according to the maximum concentrations: Fe > Zn > Ti > Mn > Cr > Hg > As > Pb > Cu, Ni, Co, Sb, Cd, Ag, Sn, and Au. Pearson correlation statistics showed strong positive relationships between Pb and Zn (r = 0.71), Pb and Cr (r = 0.57), Hg and Zn (r = 0.63), Hg and Fe (r = 0.73), Hg and Cr (r = 0.61), Zn and Fe (r = 0.69), Zn and Cr (r = 0.88), Fe and Cr (r = 0.67), and Fe and Ti (r = 0.62). Except for Pb and Cr, all the other elements had their margin of safety (MOS) values less than 100. The hazard indices (HIs) for Pb, Mn, Cr, and Ti were less than 1, indicating no risk. However, the HIs for As, Hg, Zn, and Fe were more than 1, indicating a potential risk of usage in adults. As a result, using face powders could put users at risk of exposure to trace elements. Dermal exposure to trace elements from cosmetics resulted in a lifetime cancer risk (LCR) that was higher than what was considered tolerable (LCR >10−6) due to the presence of Pb, As, and Cr. Mercury was identified as a potential skin sensitizer in the cosmetic samples examined by an exposure-based sensitization quantitative risk assessment (SQRA).