Adenosine deaminase activity modulation by some street drug: molecular docking simulation and experimental investigation

Abstract

BackgroundAdenosine deaminase (ADA) is an enzyme that plays important roles in proliferation, maturation, function and development of the immune system. ADA activity may be altered by variety of substances including synthetic or natural products. Morphine, cocaine and their analogs exert immune suppressive activities by decreasing immune system function. The purpose of this study is to confirm that this possible effect may be modulated by interaction of these substances with ADA activity by experimental and computational method.MethodsThe structural changes in ADA have been studied in presence of cocaine, ethylmorphine, homatropine, morphine and thebaine by determination of ADA hydrolytic activity, circular dichroism and fluorescence spectroscopy in different concentrations. Docking study was performed to evaluate interaction method of test compound with ADA active site using AutoDock4 software.ResultsAccording to in-vitro studies all compounds inhibited ADA with different potencies, however thebaine activated it at concentration below 50 μM, ethylmorphine inhibited ADA at 35 μM. Moreover, fluorescence spectra patterns were differed from compounds based on structural resemblance which were very considerable for cocaine and homatropine.ConclusionThe results of this study confirms that opioids and some other stimulant drugs such as cocaine can alter immune function in illegal drug abusers. These findings may lead other investigators to develop a new class of ADA activators or inhibitors in the near future.

Regulation of uric acid metabolism and excretion

“…By contrast, ibuprofen and medazepam effects on immune deficiency have been reported. This revealed that purine compound may act as ADA activator [31]. Thus, ADA, being a single chain protein, performs more than one function, consistent with the definition of a moonlighting protein.…”

“…Moreover, ADA activity changes in a variety of other diseases including acquired immunodeficiency syndrome (AIDS), anemia, various lymphomas, tuberculosis, and leukemia. On the other hand, ADA regulates the levels of endogenous adenosine which results in immune system suppression by inhibiting lymphoid or myeloid cells, including neutrophils, macrophages, lymphocytes and platelets [31].…”

A Phase 1 Study to Evaluate the Drug Interaction Between Islatravir (MK-8591) and Doravirine in Adults Without HIV

“…Doravirine is not expected to be a perpetrator of drug–drug interactions against islatravir. The effect of doravirine on the adenosine deaminase metabolic pathway is unknown, but very few drugs are known to affect this pathway [ 26 , 27 ]. To evaluate the potential of islatravir and doravirine as a combination HIV-1 treatment regimen, it is important to characterize the pharmacokinetics and safety profile when coadministered.…”

Analysis of Uric Acid Elevation

“…Hypertension is also associated with renal vasoconstriction, which causes the retention of uric acid (47). In patients receiving diuretics and antihypertensive agents for the treatment of hypertension, it was reported that the levels of uric acid increased and hyperuricemia increased to a rate of 58% (48). High uric acid levels reduce renal blood flow and GFR (49).…”