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Experimental and Computational Studies of Novel Amide Analogues of Ferulic Acid as Potential MDM2 Inhibitors to Retrieve p53 Function

SSRN, ISSN: 1556-5068
2024
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  • Usage
    135
    • Abstract Views
      109
    • Downloads
      26

Article Description

Phytochemicals are naturally occurring substances that possess heightened levels of antioxidants. Among these, ferulic acid (FA) is widely found in fruits and vegetables, including sweet corn, tomatoes, rice bran, and is recognized for its antioxidant qualities. Various diseases include cancer, cardiomyopathy, skin; brain disorders, viral infections and diabetes are the oxidative stress-based diseases could benefit from FA's treatment. However, ferulic acid's antioxidant properties were lowered by its hydophobicity, which prevents it from autoxidation of fats and oils. However, its physicochemical and pharmacological properties can be improved by the addition of amide groups which is highly desirable. In the present investigation, two new amide analogues of ferulic acid, FA2 and FA3, were designed, synthesized and screened to assess the potential of these compounds in computationaland invitro experiments. Ferulic acid analogues were biologically evaluated on K562 cells, and the results revealed that FA3, a synthesized analogue of ferulic acid, demonstrated a greater degree of inhibition that FA2 as well as the original molecule of ferulic acid, suggesting its strong antioxidant activity. Utilizing MDM2 as a receptor, we carried out docking and dynamic studies to gain an understanding of the potential molecular mechanism by which the action was carried out. The docking and dynamic results showed that FA3 has showed higher rates binding energy (-6.04Kcal/Mol) than FA2 (-4.55 04Kcal/Mol), and ferulic acid (-4.19 Kcal/Mol). All the molecules are interacted with the residues involved in p53 binding of MDM2 protein. This study clearly revealed that FA3 ferulic acid analogue interacts with MDM2 amino acids that might have inhibited by the binding of MDM2 to p53.

Bibliographic Details

Chinthakunta Naga Raju; C. Suresh Kumar; P. Mallaiah; P. Ramachandra Reddy; V. Rajani; C. M. Anuradha; P. Venkata Ramana; P. Sanjeeva; B. Subbarao; K. Yelamandra Rao

Elsevier BV

Multidisciplinary; Ferulic acid; MDM2; Molecular Docking; organic synthesis; A Analogues; Antioxidant; MTT; Dynamics simulations

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