title: Adenosine deaminase activity modulation by some street drug: molecular docking simulation and experimental investigation.
abstract: BACKGROUND
  Adenosine 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  According 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. amanlou@tums.ac.ir.
authors.forename: Massoud
authors.initials: M
authors.lastname: Amanlou
authors.forename: Ali-akbar
authors.initials: AA
authors.lastname: Saboury
authors.forename: Roya
authors.initials: R
authors.lastname: Bazl
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Ganjali
authors.forename: Shokoofeh
authors.initials: S
authors.lastname: Sheibani
mesh_terms: D000243:Adenosine Deaminase / Q000737:chemistry* / Q000378:metabolism*; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology; D000701:Analgesics, Opioid / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002942:Circular Dichroism; D004305:Dose-Response Relationship, Drug; D013287:Illicit Drugs / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D009022:Morphine Derivatives / Q000737:chemistry* / Q000494:pharmacology; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D014326:Tropanes / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000701:Analgesics, Opioid; D013287:Illicit Drugs; D009022:Morphine Derivatives; D014326:Tropanes; D000243:Adenosine Deaminase