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Albany 2019: 20th Conversation - Abstracts

category image Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

In-silico Assessment of Adenosine Receptor Ligand Binding Domain: A New Insight into Adenosine Receptor Based Therapeutics

Extracellular adenosine acts as a local modulator with a generally cytoprotective function in the body. During ischaemia or inflammation conditions adenosine levels are elevated. Among the four adenosine receptors (ARs), A2b AR expressed highly in angiogenesis during wound healing and tumor growth; its role in genetic and pharmacological studies are known to an extend (Du et al, 2015), however the binding ability of A2b with anti-angiogenic plant compounds are not well known ( Jacobson & Gao, 2006). In order to validate the usefulness of this receptor model, docking analysis of several selective and nonselective compounds were carried out to find the binding affinities and selectivity of ligands to adenosine binding region of A2b AR. Plant compounds like Chrysin, Apigenin, Theobromine, Theophylline, Genistein, Resveratrol, Pentoxifylline and synthetic compounds DAPT, SU5416, SQ22536, ZM 241385 and MSR 1754 that are known to be AR targets. Our results illustrated that A2b AR possess the strongest interaction to Chrysin with higher binding free energy score of -8.09 kcal/mol with 6-OH bond interactions at ALA82, PHE84, VAL85, ALA60, ALA64 compared to positive control of ZM241385 with -8.70 kcal/mol binding energy. Other plant molecules like resveratrol make three electrostatic interaction with GLN6, GL4, LEU2 with binding affinity of -7.04 kcal/mol of OH bond; Theobromine and theophylline similarly showed lower binding affinity of -6.448 kcal/mol and -6.41 kcal/mol. Apigenin shows -6.76 kcal/mol with 6-OH bond at THR5, LYS269, TRP270 electrostatically; Genistein shows -6.33 kcal/mol binding affinity made of 5-OH bond with LEU2 (one bonding distance), GLN6 (four bonding distance); and pentoxyflline with -6.81 kcal/mol (OH bonding) distance of 2.3 at THR139. Among the synthetic molecule DAPT with -8.35 kcal/mol binding energy making two strong OH at ASP7 two bond distance of 2.1 and 2.0; next SU5416 with -7.218 kcal/mol with TRP270 and LYS269 OH bond. Furthermore, molecular stimulation analysis might be carried out to find binding ability of the compounds tested. Based on the study result, the selected plant compounds like chrysin might considered as novel and significant compound that can be modeled and characterized for auxiliary therapeutic implement.

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This research has been supported by UGC-BSR award No: F-7-115/2007.

References

    Du, X., Ou, X., Song, T., Zhang, W., Cong, F., Zhang, S., & Xiong, Y. (2015). Adenosine A2B receptor stimulates angiogenesis by inducing VEGF and eNOS in human microvascular endothelial cells. Experimental Biology and Medicine, 240(11), 1472-1479.

    Jacobson, K. A., & Gao, Z. G. (2006). Adenosine receptors as therapeutic targets. Nature reviews Drug discovery, 5(3), 247.

Navina Panneerselvan1
Radha Madendran2
Malathi Rangunathan1

1
Department of Genetics, Dr.ALM PG IBMS, University of Madras, Taramani, Chennai-600113

1Department of Bioinformatics
Vel’s University
Velan Nagar, Pallavaram
Chennai-600117 India

Email: r_malathi@hotmail.com
navinapanneerselvan@yahoo.com