Pharmacophore Analysis and Molecular Docking Simulations to Design G Protein-coupled Receptors Antagonists with Ligand Selectivity

Document Type : Mini-reviews

Authors

1 Pharmaceutical Medicinal Chemistry, Faculty of Pharmacy, Suez Canal University

2 a. Medicinal Chemistry Department, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt b. School of Pharmacy & Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK

3 Medicinal Chemistry Department, Suez Canal University, Faculty of Pharmacy, Ismailia, Egypt

4 Faculty of Pharmacy - Suez Canal University

Abstract

Cancer development is closely associated and connected with immunosuppressive tumor microenvironment (TME) that attenuates antitumor immune responses and promotes tumor cell immunologic escape. The sequential conversion of extracellular Adenosine TriPhosphate (ATP) into adenosine by two important cell-surface ectonucleosides CD39 and CD73 plays a very critical role in reshaping the immunosuppressive TME. The accumulated extracellular adenosine mediates its regulatory functions by binding to one of four adenosine receptors (A1R, A2AR, A2BR and A3R). Adenosine emerges as a promising target for cancer therapy down to its protumor activities by inducing tumor cell proliferation, angiogenesis, chemo-resistance, and migration/invasion. Inhibition of the adenosine pathway alone or in combination with classic immunotherapies offers a potentially effective therapeutic strategy in cancer. Herein, computer-aided drug design approaches including pharmacophore analysis and molecular docking studies were adopted to examine the predicted binding modes for suggested A2A receptor antagonists to obtain a greater insight in SAR analyses and chemical examination.

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Records of Pharmaceutical and Biomedical Sciences
Volume 9, Issue 1
Chemistry
March 2025
Pages 77-83

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