title: 3-D structural interactions and quantitative structural toxicity studies of tyrosine derivatives intended for safe potent inflammation treatment.
abstract: BACKGROUND
  Drugs that inhibit cyclooxygenase-2 (COX-2) while sparing cyclooxygenase-1 (COX-1) represent a new attractive therapeutic development and offer new perspective for further use of COX-2 inhibitors. Intention of this work is to develop safer, selective COX-2 inhibitors that do not produce harmful effects.
  
  
  RESULTS
  A series of 55 tyrosine derivatives were designed for evaluation as selective COX-2 inhibitors and investigated by in silico for their anti-inflammatory activities using C-Docker. The results of docking study showed that 35 molecules were found to selectively inhibit the enzyme COX-2. These molecules formed stable π hydrophobic and additional van der Waals interactions in the active site side pocket of COX-2. The molecules selected from docking studies were examined through ADMET descriptors and Osiris property explorer to find its safety profile as well. The tyrosine derivatives containing toxic fragments were eliminated.
  
  
  CONCLUSIONS
  The results conclude that out of 55, 19 molecules possessed best binding energy (< -3.333 kcal/mol) and these molecules had more selective and safer COX-2 inhibitor profile compared to the standard celecoxib.Graphical abstract3-D structural interactions of COX-2 inhibiting tyrosine derivatives.
authors.affiliation: Drug Discovery and Development Research Group, Department of Pharmaceutical Technology, Anna University Chennai, BIT Campus, Tiruchirappalli, 620024 India.
authors.forename: Ayarivan
authors.initials: A
authors.lastname: Puratchikody
authors.affiliation: Pharmacy Group, Birla Institute of Technology and Sciences, Pilani, Hyderabad Campus, Jawahar Nagar, Secunderabad, Telangana 500 078 India.
authors.forename: Dharmaraj
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Drug Discovery and Development Research Group, Department of Pharmaceutical Technology, Anna University Chennai, BIT Campus, Tiruchirappalli, 620024 India.
authors.forename: Appavoo
authors.initials: A
authors.lastname: Umamaheswari
authors.affiliation: Drug Discovery and Development Research Group, Department of Pharmaceutical Technology, Anna University Chennai, BIT Campus, Tiruchirappalli, 620024 India.
authors.forename: Navabshan
authors.initials: N
authors.lastname: Irfan
keywords: ADMET descriptors; Anti-inflammatory; Docking; Osiris; Tyrosine derivatives