Identifying repurposed drugs as potential inhibitors of Apolipoprotein E: A bioinformatics approach to target complex diseases associated with lipid metabolism and neurodegeneration

Furkan, Mohammad; Khan, Mohd Shahnawaz; Shahwan, Moyad; Hassan, Nageeb; Yadav, Dharmendra Kumar; Anwar, Saleha; Khan, Rizwan Hasan; Shamsi, Anas

doi:10.1016/j.ijbiomac.2023.129167

Cited by 1 publication

(1 citation statement)

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“…The effective utilization of Computer-Aided Drug Design (CADD) signifies a notable advancement in drug discovery and development methodologies, offering a more cost-effective and efficient alternative to the conventional processes acknowledged for their prohibitive costs and time requirements. Recent progress in in-silico techniques has enabled the construction of physicochemical models to simulate biomolecular processes, empowering numerous research laboratories to innovate and discover novel medications [ 24 ]. Through CADD approaches, several potent and commonly prescribed drugs have been successfully developed to combat various life-threatening illnesses and pathogenic infections such as Human Immunodeficiency Virus (HIV), Influence Virus, Hepatitis C etc.…”

Section: Introductionmentioning

confidence: 99%

Unveiling potent inhibitors for schistosomiasis through ligand-based drug design, molecular docking, molecular dynamics simulations and pharmacokinetics predictions

Ja’afaru,

Uzairu,

Bayil

et al. 2024

PLoS ONE

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Schistosomiasis is a neglected tropical disease which imposes a considerable and enduring impact on affected regions, leading to persistent morbidity, hindering child development, diminishing productivity, and imposing economic burdens. Due to the emergence of drug resistance and limited management options, there is need to develop additional effective inhibitors for schistosomiasis. In view of this, quantitative structure-activity relationship studies, molecular docking, molecular dynamics simulations, drug-likeness and pharmacokinetics predictions were applied to 39 Schistosoma mansoni Thioredoxin Glutathione Reductase (SmTGR) inhibitors. The chosen QSAR model demonstrated robust statistical parameters, including an R2 of 0.798, R2adj of 0.767, Q2cv of 0.681, LOF of 0.930, R2test of 0.776, and cR2p of 0.746, confirming its reliability. The most active derivative (compound 40) was identified as a lead candidate for the development of new potential non-covalent inhibitors through ligand-based design. Subsequently, 12 novel compounds (40a-40l) were designed with enhanced anti-schistosomiasis activity and binding affinity. Molecular docking studies revealed strong and stable interactions, including hydrogen bonding, between the designed compounds and the target receptor. Molecular dynamics simulations over 100 nanoseconds and MM-PBSA free binding energy (ΔGbind) calculations validated the stability of the two best-designed molecules. Furthermore, drug-likeness and pharmacokinetics prediction analyses affirmed the potential of these designed compounds, suggesting their promise as innovative agents for the treatment of schistosomiasis.

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Section: Introductionmentioning

confidence: 99%