In silico study of thymohydroquinone interaction with blood-brain barrier disrupting proteins

Aim:To evaluate the inhibitory interaction of thymohydroquinone against blood-brain barrier (BBB)-associated neuropsychiatric and neurodegenerative disorders.Materials & methods:An elaboratedin silicostudy was designed to evaluate the interaction of thymohydroquinone with BBB-disrupting proteins and to highlight its pharmacokinetic and safety attributes.Results:Thymohydroquinone demonstrated stable interaction with BBB-disrupting protein active site with Ki (inhibition constant) ranges of (2.71 mM-736.15 mu M), binding energy (-4.3 to 5.6 Kcal/mol), ligand efficiency (-0.36 to 0.42 Kcal/mol) and root mean square deviation value of (0.80-2.59 angstrom).Conclusion:Further pharmacokinetic analysis revealed that thymohydroquinone is BBB and central nervous system (CNS) permeant with high acute toxicity and could be a candidate drug for the treatment of these neurological conditions. Lay abstract: The blood-brain barrier (BBB) is a complex neurological barrier whose disruption is associated with the development and exacerbation of different neurodegenerative and neuropsychiatric diseases. There are several drug candidates available that provide symptomatic treatment but have low BBB and central nervous system (CNS) permeability. Thymohydroquinone, a renowned medicinal compound has demonstrated a promising role in inhibiting BBB-disrupting proteins by forming hydrogen bonds with the active subunits with great stability and efficiency, thus, outcompeting its natural substrate. Through pharmacokinetic investigation, it was proven that thymohydroquinone has high BBB and CNS permeability with appropriate acute toxicity and adverse effects profiles.