Browsing by Author "Ibrahim NO"

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    Consensus scoring-based virtual screening and molecular dynamics simulation of some TNF-alpha inhibitors
    (2022) Boyenle ID; Adelusi TI; Ogunlana AT; Oluwabusola RA; Ibrahim NO; Tolulope A; Okikiola OS; Adetunji BL; Abioye IO; Kehinde Oyedele AQ
    Inhibition of Tumor Necrosis Factor-alpha (TNF-alpha) represents a therapeutic approach towards the management or treatment of various inflammatory diseases like rheumatoid arthritis and cancer, but the current treatment regimen against this target in these diseases is the use of antibodies which may trigger an autoimmune response. This suggests a search for small-molecule inhibitors that could selectively inhibit the protein target. In the present study, fifty-five bioactive compounds of plant origin with already reported anti-inflammatory activities were screened for their affinity for TNF-alpha using a molecular docking strategy. We combined results from three different software packages (iGEMDOCK, MOE, & SAMSON) to come up with the best binders of the target. In addition, the resulting binders were subjected to in silico ADMET (Absorption, distribution, metabolism, excretion, and toxicity) and 100 ns molecular dynamics simulation to determine their drug-like properties and atomistic binding mechanisms respectively. Of the fifty-five evaluated bioactive compounds, Rutin, Schisantherin A, and Hesperidin performed well in the three software packages, with considerable ranking therewith. Interestingly, these compounds did not only interact with hotspot residues on TNF-alpha but also apparently balanced well on the knife-edge of pharmacokinetics and toxicity. More importantly, from the RMSD, RMSF, ROG, SASA, and hydrogen bond analysis, it was seen that Rutin, Schisantherin A, & Hesperidin exhibited stability in the active pocket of the protein. These results portend the three compounds as potent inhibitors of TNF-alpha that should be considered for further evaluation and drug development.
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    Dynamics of pentavalent inorganic arsenic effects on some glycolytic and mitochondrial energy metabolizing enzymes in male Wistar rats
    (2022) Fatoki JO; Alabi IA; Atere TG; Ibrahim NO; Onifade EA; Ojokuku OF; Abdulateef MA; Abisoye OA; Raji PK; Adeniyi A; Ademuyiwa DF; Fatoki CO; Oyewo EB; Badmus JA
    Exposure to environmental toxicants such as arsenic presents serious health challenges to humans. The effects of arsenic have been extensively evaluated, but there is a dearth of scientific findings on its effects on some key enzymes of glycolysis, Krebs cycle, and electron transport chain. This study, therefore, is aimed at investigating the time-course effects of arsenic exposure on these key enzymes in male Wistar rats. Rats (n = 45) were exposed to arsenic (100, 150, and 200 ppm) for 4, 8, and 12 weeks respectively in their drinking water. Control rats (n = 5) received drinking water for 12 weeks, after which blood and liver were removed from the animals and analyzed for some energy metabolizing enzymes spectrophotometrically. Data were analyzed using one-way analysis of variance followed by Tukey's post hoc test and p < 0.05 was considered significant. Our findings showed that arsenic exposure reduced the activities of plasma hexokinase at weeks 4, 8, and 12. Meanwhile, erythrocyte and liver homogenate hexokinase were significantly (p < 0.05) enhanced only at week 4. Plasma and liver aldolase activities were significantly (p < 0.05) induced at week 4, while aldolase activities of other compartments were significantly (p < 0.05) reduced at weeks 4, 8, and 12. In addition, arsenic significantly (p < 0.05) increased the activity of lactate dehydrogenase in various tissue compartments, effects of arsenic exposure were characterized by a significant (p < 0.05) decrease in the activities of malate dehydrogenase, complexes of the electron transport chain when compared with the control animals in all the tissues. These findings indicated that arsenic exposure induced various compartment-specific modulation of key enzymes of glycolysis, Krebs cycle and electron transport chain. This might be one of the mechanisms through which arsenic mediates its toxicity and its associated disease endpoints.