A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study

A merged pharmacophore model based on the most potent non-nucleoside inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and natural products were generated and applied for compounds filtration. The effects of filtrated compounds based on pharmacophore and docking studies investigated on ADA by UV and Fluorescence spectroscopy techniques.Extracted compounds were find efficiently inhibit ADA, and the most potent (2) shows an inhibition constant equal to 20 μM. Besides, Fluorescence spectroscopy studies revealed that enzyme 3D structure bear further change in lower concentrations of compound 2.3 non-nucleoside inhibitors for ADA are presented. According to obtained results from UV and fluorescence spectroscopy, such interesting pharmacophore template with multiple approaches will help us to extract or design compound with desired properties.Adenosine deaminase (ADA) is a key enzyme in the purine metabolism that hydrolyse adenosine to inosine irreversibly [1]. This path involves in RNA, DNA, ATP synthesizes, and energy transitions reactions. This enzyme also has been found in lymphoid systems like lymph nodes, spleen and thymus [2]. Involvement of this enzyme is clear in catabolytic paths and also its role in the protection of immune systems [3-5].Over activity of ADA is associated with AIDS, leukemia, stresses and Parkinson [6-8]. In addition, the high value of ADA has been seen in rheumatoid arthritis [9]. Adenosine as the substrate of ADA regulates many of physiological processes in different organisms [10,11]. Adenosine influences deeply on hypertension, sedation and vessels dilatation [12]. Also, it acts as nerve modulators or as neural hormones [13].On the other hand, most of adenosine analogues have more importance in chemotherapy, cancer, immunology, virology and parasitology, which could be deaminated by the enzyme and deactivated through their metabolic pathway [14]. So, inhibition of ADA can solve mentioned problems [15,16]. Till now, suggested inhibitors