Browsing by Author "Adelusi TI"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    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.
  • Thumbnail Image
    Item
    Molecular dynamics, quantum mechanics and docking studies of some Keap1 inhibitors – An insight into the atomistic mechanisms of their antioxidant potential
    (2021) Adelusi TI; Abdul-Hammed M; Idris MO; Oyedele QK; Adedotun IO
    Inhibitors of Keap1 would disrupt the covalent interaction between Keap1 and Nrf2 to unleash Nrf2 transcriptional machinery that orchestrates its cellular antioxidant, cytoprotective and detoxification processes thereby, protecting the cells against oxidative stress mediated diseases. In this in silico research, we investigated the Keap1 inhibiting potential of fifty (50) antioxidants using pharmacokinetic ADMET profiling, bioactivity assessment, physicochemical studies, molecular docking investigation, molecular dynamics and Quantum mechanical-based Density Functional Theory (DFT) studies using Keap1 as the apoprotein control. Out of these 50 antioxidants, Maslinic acid (MASA), 18-alpha-glycyrrhetinic acid (18-AGA) and resveratrol stand out by passing the RO5 (Lipinski rule of 5) for the physicochemical properties and ADMET studies. These three compounds also show high binding affinity of -10.6 kJ/mol, -10.4 kJ/mol and -7.8 kJ/mol at the kelch pocket of Keap1 respectively. Analysis of the 20ns trajectories using RMSD, RMSF, ROG and h-bond parameters revealed the stability of these compounds after comparing them with Keap1 apoprotein. Furthermore, the electron donating and accepting potentials of these compounds was used to investigate their reactivity using Density Functional Theory (HOMO and LUMO) and it was revealed that resveratrol had the highest stability based on its low energy gap. Our results predict that the three compounds are potential drug candidates with domiciled therapeutic functions against oxidative stress-mediated diseases. However, resveratrol stands out as the compound with the best stability and therefore, could be the best candidate with the best therapeutic efficacy.