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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. amanlou@tums.ac.ir.
Roya
R
Bazl
Mohammad Reza
MR
Ganjali
Ali-Akbar
AA
Saboury
Alireza
A
Foroumadi
Parviz
P
Nourozi
Massoud
M
Amanlou