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

Abstract

Background and the purpose of the studyAdenosine deaminase (ADA) inhibition not only may be applied for the treatment of ischemic injury, hypertension, lymphomas and leukaemia, but also they have been considered as anti- inflammatory drugs. On the other hand according to literatures, ADA inhibitors without a nucleoside framework would improve pharmacokinetics and decrease toxicity. Hence we have carried out a rational pharmacophore design for non-nucleoside inhibitors filtration.MethodsA 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.ResultsExtracted 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.Conclusion3 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.

Role of Copper in the Onset of Alzheimer’s Disease Compared to Other Metals

“…On the other hand, ADA acts as an allosteric modulator of adenosine receptors ( Cortés et al, 2015 ). Because of ADA’s involvement in different health disorders, the development of ADA inhibitors as feasible therapeutic agents has been considered in many studies ( Cristalli et al, 2001 ; Saboury et al, 2003 , 2004 , 2005 ; Ataie et al, 2004 , 2007 ; Terasaka et al, 2004a , b ; Da Settimo et al, 2005 ; Ajloo et al, 2007 ; Ujjinamatada et al, 2008 ; La Motta et al, 2009 ; Bazl et al, 2012 ). Recently, ADA inhibitors have been proposed in perinatal hypoxia–ischemia brain injury treatment ( Pimentel et al, 2013 ).…”

The effect of adenosine deaminase inhibition on the A1 adenosinergic and M2 muscarinergic control of contractility in eu- and hyperthyroid guinea pig atria

“…Thus, to elevate the interstitial adenosine concentration, ADA inhibition appears to be an intervention more reliable than nucleoside transport blockade. It should be noted that ADA inhibitors have a wide range of actions throughout the body that forms the basis for several side effects (Bazl et al 2012 ). However, these side effects are less problematic if ADA inhibitors are applied in an isolated organ rather than the whole body, e.g., in a heart to be transplanted.…”