Pharmacophore modeling, molecular docking, QSAR, and in silico ADMET studies of gallic acid derivatives for immunomodulatory activity.
Immunomodulation refers to an alteration in the immune response due to the intrusion of foreign molecules into the body. In the present communication, QSAR and docking studies of gallic acid derivatives were performed in relation to their immunomodulatory activities. Screening through the use of a QSAR model suggested that the compounds G-4, G-7, G-9, G-10, G-12, and G-13 possess immunomodulatory activity. Activity was predicted using a statistical model developed by the forward stepwise multiple linear regression method. The correlation coefficient (r(2)) and the prediction accuracy (rCV(2)) of the QSAR model were 0.99 and 0.96, respectively. The QSAR study indicated that chemical descriptors-dipole moment, steric energy, amide group count, λ(max) (UV-visible) and molar refractivity-are well correlated with activity, while decreases in the dipole moment, steric energy, and molar refractivity were negatively correlated. A molecular docking study showed that the compounds had high binding affinities for the INFα-2, IL-6, and IL-4 receptors. Binding site residues formed H-bonds with the designed gallic acid derivatives G-3, G-4, G-5, G-6, G-7, and G-10. Moreover, based on screening for oral bioavailability, in silico ADME, and toxicity risk assessment, we concluded that compound G-7 exhibits marked immunomodulatory activity, comparable to levamisole.
Metabolic and Structural Biology Department, Council of Scientific and Industrial Research, Central Institute of Medicinal and Aromatic Plants, Lucknow, UP, India.
Dharmendra Kumar
DK
Yadav
Feroz
F
Khan
Arvind Singh
AS
Negi
D000465:Algorithms; D020816:Amino Acid Motifs; D001665:Binding Sites; D001682:Biological Availability; D003198:Computer Simulation; D015195:Drug Design; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D006801:Humans; D006860:Hydrogen Bonding; D007155:Immunologic Factors / Q000737:chemistry*; D008956:Models, Chemical; D008958:Models, Molecular; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D018121:Receptors, Cytokine / Q000737:chemistry; D013816:Thermodynamics
D007155:Immunologic Factors; D018121:Receptors, Cytokine; D005707:Gallic Acid