In-Silico Analysis and Molecular Docking Studies of Potential Phosphodiesterase 4 Inhibitors using Ventilago Isolates

Title:In-Silico Analysis and Molecular Docking Studies of Potential Phosphodiesterase 4 Inhibitors using Ventilago Isolates

Volume: 15 Issue: 9

Author(s): A.A. Manakadan, S. Sathianarayanan*, P.K. Krishnan Namboori and T.S. Saranya

Affiliation:

• Department of Pharmaceutical Chemistry, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Ponekkara, Kochi, Pin Code-682041, Kerala,India

Keywords: Ventilago isolates, molecular docking, PDE4 inhibitors, drug-likeness, apremilast, docking score.

Abstract: Diverse pathways and inflammatory responses are controlled by cAMP which is a vital intracellular second messenger. The cAMP is suppressed by the enzyme Phosphodiesterase4 (PDE4) specifically PDE4B2, which is the target proteins articulated in the inflammatory cells, for instance, T cells and monocytes in the pathogenesis of diseases such as asthma, rheumatoid arthritis, COPD and multiple sclerosis. PDE4 inhibition leads to the enhancement of cAMP level, resulting in the downregulation of these diseases. In this investigation, docking analysis, ADMETox and drug-likeness have been conducted for the analysis of protein lead interaction and to check whether ventilago isolates can behave as potential ligands with pharmacological activity as PDE4 inhibitors. From this study, it has been established that 1RO6 and 1RO9 proteins have more stability than the other proteins. 34 Ventilago phytoconstituent isolates with five different organic nucleuses such as isofuranonaphthoquinones, anthraquinones, benzisochromanquinones, naphthalene, and naphthoquinones are used for the analysis. The in-silico studies displayed considerable binding affinity of ventilago isolates with the protein and accordingly, the ventilago isolates having anthraquinones nuclei like Calyculatone, 4,5-dihydroxynordigitoleutein and 2-hydroxyislandicin and the phytoconstituents containing naphthaquinones nucleus Cordeauxione possess the highest PDE4 inhibitory activity as they gave a strong hydrogen bonding profile with the amino acid residues of the target protein. The computational study provides evidence that the ventilago isolates can be used as valuable ligands with comparable PDE4 inhibitory activity as that of the standard drug Apremilast and further in vitro and in vivo investigations may prove its therapeutic potential.

Cite this article as:

Manakadan A.A., Sathianarayanan S. *, Namboori Krishnan P.K. and Saranya T.S., In-Silico Analysis and Molecular Docking Studies of Potential Phosphodiesterase 4 Inhibitors using Ventilago Isolates, Letters in Organic Chemistry 2018; 15 (9) . https://dx.doi.org/10.2174/1570178615666180430120235