Abstract
The lipophilic derivative of thalidomide (4-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)-N′-[(4-ethoxyphenyl)methylidene]benzohydrazide, 6P) was synthesized to enhance its characteristics and efficacy. Earlier studies have proved the immunomodulatory and anti-inflammatory effects of 6P. In this study the interaction between bovine serum albumin (BSA) and 6P was studied using a multi-spectroscopic approach which included UV spectrophotometry, spectrofluorimetry and three dimensional spectrofluorometric and molecular docking studies. Static quenching was involved in quenching the fluorescence of BSA by 6P, because a complex formation occurred between the 6P and BSA. The binding constant decreased with higher temperature and was in the range of 2.5 × 105–4.8 × 103 L mol−1 suggesting an unstable complex at higher temperatures. A single binding site was observed and the the site probe experiments showed site II (sub-domain IIIA) of BSA as the binding site for 6P. The negative values of ∆G0, ∆H0 and ∆S0 at (298/303/308 K) indicated spontaneous binding between 6P and BSA as well as the interaction was enthalpy driven and van der Waals forces and hydrogen bonding were involved in the interaction. The docking results and the results from the experimental studies are complimentary to each other and confirm that 6P binds at site II (sub-domain IIIA) of BSA.
Highlights
Thalidomide and its various derivatives are used as prophylactic drugs in the case of autoimmune diseases due to their immunomodulatory and anti-inflammatory properties [1]
The results show a decrease in the Kb values with an increase in temperature, demonstrating the instability of the 6P-bovine serum albumin (BSA) complex at higher temperatures
A correlation coefficient (r2 ) of >0.99 at all the three studied temperatures indicates that the interaction between 6P and BSA followed a binding model based on the double log regression method
Summary
Thalidomide and its various derivatives are used as prophylactic drugs in the case of autoimmune diseases due to their immunomodulatory and anti-inflammatory properties [1]. 22 of of 10 other adverse events caused by thalidomide several structural analogues were synthesized and these pain [6,7,8,9].less. Structural modification of thalidomide has produced thalidomide several structural analogues were synthesized and these exhibited less toxicity and were potent inhibitors of TNF-α [10,11]. Structural modification thalidomidederivative has produced potent inhibitors of TNF-α [10,11]. Potent anti-inflammatory effects of theexamination compound alsoCompound confirmed the effects thecapability compoundto6P.bind. NF-κB p65, 1MY5 transcription factor NF-κB p65, 1MY5 PDB-structure, etc., increasing its anti-inflammatory. Figure structure of ofthe thelipophilic lipophilicthalidomide thalidomidederivative derivative(4-(1,3-dioxo-1,3-dihydro-2H(4-(1,3-dioxo-1,3-dihydro-2HFigure 1
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