title: New Insight into the SAR of Pyrimido [4,5-b][1,4] Benzothiazines as 15-lipoxygenase Inhibitors.
abstract: OBJECTIVE
  Recently we reported that the soybean 15-lipoxygenase (SLO) inhibitory activity of pyrimido[4,5-b][l,4]benzothiazines largely depends on the orientation of sulfur atom of thiazine core towards Fe(III)-OH in the active site pocket of the enzyme with subsequent oxidation of sulfur to sulfoxide. In this paper the results of a comparative study on the SLO inhibitory activities of the mentioned compounds using ab initio calculations and docking analyses has been reported.
  
  
  METHODS
  Structure optimization and docking analyses were performed using HyperChem 7.5 and AutoDock Tools 4.0 respectively. Enzyme assessment was reduced using spectrophotometric MBTH-DMAB method. Results : The inhibitory activity of synthetic 2-substituted pyrimido[4,5-b][l,4]benzothiazines against soybean 15-lipoxygenase (SLO) was evaluated and structure activity relationships and binding modes of their 4-H and 4-methyl analogs were studied using docking analysis and ab initio calculations.
  
  
  CONCLUSIONS
  The results of these studies showed that the lack of 4-methyl substituent in the pyrimido[4,5-b][1,4]benzothiazine molecules greatly reduces their lipoxygenase inhibitory activities and it was also found that the HOMO energy difference between the 4-H and 4-Methyl analogs can be responsible for the observed inhibitory activity reduction.
  
  
  CONCLUSIONS
  Our molecular modeling studies shows that by using more flexible amino acids during the docking process, more rational results can be obtained. The method of measuring the lipoxygenase activity is also of prime importance for the study of structure activity relationship.
authors.affiliation: Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad, IR Iran.
authors.forename: Nona
authors.initials: N
authors.lastname: Pooryaghoobi
authors.forename: Mehdi
authors.initials: M
authors.lastname: Bakavoli
authors.forename: Maliheh
authors.initials: M
authors.lastname: Alimardani
authors.forename: Tahmineh
authors.initials: T
authors.lastname: Bazzazan
authors.forename: Hamid
authors.initials: H
authors.lastname: Sadeghian
keywords: DMAB; Docking; MBTH; Peroxide formation; SLO