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"Njogu, Kimani"
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Galantamine Based Novel Acetylcholinesterase Enzyme Inhibitors: A Molecular Modeling Design Approach
Acetylcholinesterase (AChE) enzymes play an essential role in the development of Alzheimer’s disease (AD). Its excessive activity causes several neuronal problems, particularly psychopathies and neuronal cell death. A bioactive pose on the hAChE B site of the human acetylcholinesterase (hAChE) enzyme employed in this investigation, which was obtained from the Protein Data Bank (PDB ID 4EY6), allowed for the prediction of the binding affinity and free binding energy between the protein and the ligand. Virtual screening was performed to obtain structures similar to Galantamine (GNT) with potential hAChE activity. The top 200 hit compounds were prioritized through the use of filters in ZincPharmer, with special features related to the pharmacophore. Critical analyses were carried out, such as hierarchical clustering analysis (HCA), ADME/Tox predictions, molecular docking, molecular simulation studies, synthetic accessibility (SA), lipophilicity, water solubility, and hot spots to confirm the stable binding of the two promising molecules (ZINC16951574-LMQC2, and ZINC08342556-LMQC5). The metabolism prediction, with metabolites M3-2, which is formed by Glutathionation reaction (Phase II), M1-2, and M2-2 formed from the reaction of S-oxidation and Aliphatic hydroxylation (Phase I), were both reactive but with no side effects. Theoretical synthetic routes and prediction of synthetic accessibility for the most promising compounds are also proposed. In conclusion, this study shows that in silico modeling can be used to create new drug candidate inhibitors for hAChE. The compounds ZINC16951574-LMQC2, and ZINC08342556-LMQC5 are particularly promising for oral administration because they have a favorable drug-likeness profile, excellent lipid solubility, high bioavailability, and adequate pharmacokinetics.
Journal Article
Discovery of α-amylase and α-glucosidase dual inhibitors from NPASS database for management of Type 2 Diabetes Mellitus: A chemoinformatic approach
Postprandial hyperglycemia, typical manifestation of Type 2 Diabetes Mellitus (T 2 DM), is associated with notable global morbidity and mortality. Preventing the advancement of this condition by delaying the rate of glucose absorption through inhibition of α-amylase and α-glucosidase enzymatic activities is of utmost importance. Finding a safe antidiabetic drug is essential since those that are currently on the market have drawbacks like unpleasant side effects. The current study utilized computer-aided drug design (CADD), as a quick and affordable method to find a substitute drug template that can be used to control postprandial hyperglycemia by modulating the activity of α-amylase and α-glucosidase enzymes. The Natural Products Activity and Species database (NPASS) (30,926 compounds) was screened in silico , with a focus on evaluating drug-likeness, toxicity profiles and ability to bind on a target protein. Two molecules NPC204580 (Chrotacumine C) and NPC137813 (1-O-(2-Methoxy-4-Acetylphenyl)-6-O-(E-Cinnamoyl)-Beta-D-Glucopyranoside) were identified as potential dual inhibitors for α-amylase and α-glucosidase with free binding energies of -14.46 kcal/mol and -12.58 kcal/mol for α-amylase, and -8.42 kcal/mol and -8.76 kcal/mol for α-glucosidase, respectively. The molecules showed ionic, H-bonding and hydrophobic interactions with critical amino acid residues of both enzymes. Moreover, 100 ns molecular dynamic simulations showed that both molecules are stable on the receptors’ active sites based on root mean square deviation (RMSD), root mean square fluctuation (RMSF), and the Generalized Born surface area (GBSA) energy calculated. The two compounds are thus promising therapeutic agents for T 2 DM that merit further investigation due to their excellent binding energies, encouraging pharmacokinetics, toxicity profiles, and stability as demonstrated in simulated studies.
Journal Article
Elucidating the functions of gut microbiota from two edible dung beetle species: Implications for waste management and food industry
Dung beetle larvae are consumed globally, yet their gut microbiota across different geographical locations remains largely unexplored. This study examined the diversity and composition of the gut microbiota of two edible dung beetle species, Cetonia aurata and Rhinoceros beetle ( Oryctes sp.), from three sites in Kenya. Using advanced molecular techniques, bacterial and fungal communities were sequenced. The most abundant bacterial phyla in C. aurata were Firmicutes (42.10%) and Bacteroidota (32.50%), while Oryctes sp. had higher levels of Proteobacteria (35.00%), Actinobacteriota (11.40%) and Desulfobacterota (7.40%). Fungal communities were dominated by Lecanoromycetes (92.60%) in Oryctes sp. and Saccharomycetes (92.60%) in C. aurata . Beta diversity analysis revealed that neither species phylogeny nor larval location significantly influenced the presence of specific microbes. Pathways related to nitrogen and carbon degradation were predicted in bacteria like Bacillus , Pseudomonas mosselii , and Proteiniphilum . This implies that bacteria and fungi from the gut of dung beetle larvae could be ideal targets for potential bio‐resource to eliminate waste pollution and opened an important window of opportunity for bio-based economy solutions. This work offers very practical solutions that have great business potential that can create a gigantic market ranging from functional foods to dietary supplements and therapeutic applications.
Journal Article
Natural Pesticides in Crop Protection: Comparative Advantages, Ecological Risks, and Future Directions
Although synthetic pesticides have long been used to protect crops, their widespread use has led to significant health and environmental problems, including ecological contamination, resistant pest populations, and hazardous residues in food. These restrictions have sparked interest in natural pesticides (NPs), particularly the secondary metabolites of plants, which can offer less persistent and biodegradable alternatives. However, each compound must be assessed for bioactivity, selectivity, and ecological impact; natural origin does not guarantee environmental safety or pesticidal appropriateness. This review highlights the pesticidal potential of five major classes of natural products: alkaloids, flavonoids, terpenoids, steroids, and phenolic compounds. Alkaloids such as berberine and matrine exhibit strong antifungal and insecticidal activities, while flavonoids such as quercetin derivatives suppress bacterial pathogens, including Xanthomonas spp. Terpenoids such as thymol inhibit fungal pathogens, including Rhizoctonia solani and Fusarium oxysporum, and phenolics such as resveratrol contribute to resistance against Botrytis cinerea. Natural steroids provide additional antifungal and insecticidal efficacy. All these cases show that NPs are interesting instruments for sustainably protecting crops, although there are still issues with formulation optimization, toxicity assessment, and economic viability. To close these gaps and make it possible to include natural insecticides in standard agricultural practices, more studies are necessary.
Journal Article
A review and in silico screening of plant-derived snake venom/toxin inhibitors: ADMET, drug-likeness, and medicinal chemistry profiling
Snakebite envenomation remains a pressing global health issue, contributing to high rates of illness and death. It also imposes significant socio-economic burdens on affected communities. Recent conservative estimates suggest that approximately 5.4 million snakebite incidents occur annually, leading to nearly 138,000 fatalities. In Africa alone, as many as 500,000 cases are documented each year. This research seeks to explore phytochemicals reported to exhibit in vitro and in vivo inhibitory effects on snake venom and toxin targets. A systematic review was conducted utilizing six electronic databases for literature searches, including Google Scholar, Web of Science, ScienceDirect, Scopus, Springer, and PubMed. This process identified 213 phytocompounds with inhibitory activity against the specified targets. Computational tools such as SwissADME, pkCSM, ADMETlab, ProTox3, Toxtree, and DataWarrior were employed to assess the absorption, distribution, metabolism, excretion, and toxicity (ADMET) characteristics, alongside other medicinal chemistry properties of these compounds. The results indicate that several plant-derived molecules effectively inhibit snake venom/toxin targets in vitro and in vivo ; however, only a few appear suitable for drug development without further modifications. Among the analyzed compounds, the terpenes labdane lactone and labdane trialdehyde, along with the benzenoid anisic acid, exhibited strong antivenom potential. Notably, anisic acid achieved complete (100%) neutralization of lethality and defibrinogenation induced by the venoms of Naja kaouthia , Daboia russelii , Ophiophagus hannah , and Echis carinatus in both in vivo and in vitro studies. Labdane lactone and labdane trialdehyde, which were isolated from Curcuma antinaia and Curcuma zedoaroides , respectively, demonstrated significant venom-inhibitory activity at a concentration of 22.7 μM and 21.9 μM against Ophiophagus hannah venom. Specifically, labdane lactone exhibited an inhibition rate of 83%, while labdane trialdehyde achieved a 62% inhibition rate against the venom of Ophiophagus hannah along with favorable in silico drug-likeness and ADMET profiles.
Journal Article
Nutritional composition of edible wood borer beetle larvae in Kenya
Exploration of edible insects as sustainable alternative nutrient-dense sources such as nutraceuticals have attracted more and more global attention recently. However, research on wood borer beetles have largely been overlooked. This study assessed the entomo-chemical properties of Titoceres jaspideus (Cerambycidae) and Passalus punctiger (Passalidae), which are widely consumed in many African countries, including Kenya. The crude protein content of the beetle larvae ranged between 27.5–39.8 mg BSA/g. In comparison with those of cereals, amino acids such as lysine (7.9–9.9 mg/g), methionine (0.48–0.64 mg/g) and threonine (2.31–2.55 mg/g) were considerably high in the larvae. Methyl-5 Z ,8 Z ,11 Z ,14 Z -eicosatetraenoate and methyl-9 Z -octadecenoate were the predominant polyunsaturated and monounsaturated fatty acids, respectively. High total phenols (>4.4 mg GAE/g), flavonoids (>3.6 mg QE/g) and anti-oxidative activities (>67%) were recorded for both larvae. This implies that increasing the consumption of wood-borer beetle larvae would positively impact the state of the natural environment and reduce the problem of malnutrition in the society. Thus, applying these strategies to develop insect food in a more familiar form can help to make insect-enriched foods more appealing to consumers, facilitating their widespread adoption as a sustainable and nutritious food source.
Journal Article
Novel Haloalkaliphilic Nitrile‐Degrading Bacteria From Soda Lake Soil of Rift Valley Kenya
Nitrile biotransformation has garnered significant attention in recent years due to its widespread applications in various industries. This study is aimed at investigating the ability of haloalkaliphilic bacteria from extremely haloalkaline lakes in Kenya to produce unique nitrilases with nitrile-degrading potential.
A combination of enrichment and isolation was done on a mineral supplemented with either butyronitrile or isobutyronitrile, colorimetric assays, nesslerization method, Bertholet reaction, and molecular characterization.
Sixty bacterial isolates were recovered, of which 14 exhibited 6 nitrilase and 8 nitrile hydratase enzyme activities. The isolates, affiliated with
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,
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,
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sp. YIM,
sp. AKP2, and
species, demonstrated optimal growth at pH 8.0-9.0, 5% salt concentration, and 28°C-40°C temperature. Notably, the nitrilase and nitrile hydratase enzymes exhibited optimal pH activity at 7.0-7.5.
This study identifies novel bacterial isolates from Kenyan soda lakes with the ability to produce nitrilase and nitrile hydratase enzymes, which can be utilized for the hydrolysis of nitrile to carboxylic acid, ammonia, and amide.
The identification of bacterial strains capable of degrading nitriles into acids and amide compounds that are environmentally safe and beneficial to the green industry highlights a promising approach for mitigating the harmful effects of toxic nitriles in the environment. Biodegradation of nitriles by bacteria from soda lakes offers a sustainable solution to reduce ecological damage. Techniques such as enzymatic assays, colorimetric methods, the Berthelot reaction, and the two-step nesslerization method are essential for isolating and characterizing nitrile-degrading bacteria. The discovery of these biocatalysts not only advances green catalyst research but also holds significant potential for applications in organic synthesis, biotechnology, and environmental remediation.
Journal Article
Antiprotozoal Aminosteroid Alkaloids from Buxus obtusifolia (Mildbr.) Hutch
Human African Trypanosomiasis (HAT; sleeping sickness) and Malaria are life-threatening protozoan infections in tropical regions, with limited treatment options. As part of our ongoing efforts to discover new aminosteroid alkaloids from the Buxaceae family with antiprotozoal activity, which might serve as leads to new drugs against these infections, we investigated the dichloromethane extract from the leaves of Buxus obtusifolia (Mildbr.) Hutch. collected in Kenya, a species native to Kenya and Tanzania. To the best of our knowledge, and based on the most recent comprehensive literature review, this study represents the first phytochemical investigation of this plant. The alkaloid-enriched fraction yielded a total of 24 aminosteroid alkaloids, including 18 hitherto undescribed compounds (2, 3, 5–9, 11, 12, 15–19, and 21–24), along with six known compounds, two of which (1 and 4) are described as constituents of a natural source for the first time. Obtusiaminocyclin (24) represents the first Buxus alkaloid with a novel carbocyclic steroid skeleton with a cyclopropane ring comprising C-9, C-19 and C-11 accompanied by an unprecedented amino bridge between C-3 and C-10. The structures of the isolated compounds were determined using UHPLC/+ESI-QqTOF-MS/MS and NMR spectroscopy. The total crude extract, the alkaloid-enriched fraction, CPC subfractions and all isolated compounds were tested for in vitro antiprotozoal activity against Trypanosoma brucei rhodesiense (Tbr, responsible for East African HAT) and Plasmodium falciparum (Pf, responsible for tropical Malaria) as well as cytotoxicity against mammalian cells (L6 cell line). Deoxycyclovirobuxeine-B (12) (IC50 = 0.8 µmol/L, SI = 108) and 29-trimethoxybenzoyloxy-obtusibuxoline (5) (IC50 = 0.5 µmol/L, SI = 11) showed the highest activities with good selectivity indices against Tbr and Pf, respectively. Consequently, our findings provide valuable aminosteroid candidates that can serve as promising leads in our ongoing search for new drugs against HAT and Malaria.
Journal Article
Correction: Mukavi et al. Antiprotozoal Aminosteroid Alkaloids from Buxus obtusifolia (Mildbr.) Hutch. Molecules 2025, 30, 4558
In the original publication [...]
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