title: Atom level electrotopological state indexes in QSAR: designing and testing antithyroid agents.
abstract: OBJECTIVE
  To design antithyroid agents with less side effects, the electrotopological-state (E-state) indexes of thiourylene moiety (SN&S) was utilized as a guideline to develop five acrylic thiourylene-type compounds with reduced antioxidant property.
  
  
  METHODS
  These agents were synthesized and screened for antithyroid activity in rats using 125I-thiocyanate discharge technique. In addition, chemiluminescence studies on the activated polymorphonuclear leukocytes (PMNLs) were also conducted to reveal antioxidant properties of the tested compounds.
  
  
  RESULTS
  A linear relationship between the in vitro literature value of the formation constants of thiourylene-type compounds with iodine (Kc) and the SN&S was observed and utilized in designing those agents. At least one of the compounds (abouthiouzine) was found to have a potential value as an antithyroid agent. The relative efficacy of abouthiouzine [1-n-butyl-3(isonicotinamido)-2-thiourea], after equimolar dose, was 102% and 51.5% of that of propylthiouracil with respect to the rate of 125I-discharge and 125I-uptake, respectively. In addition, chemiluminescence studies on PMNLs revealed that abouthiouzine has slight oxidant property. Such properties may provide advantages in avoiding the iatrogenic hypothyroidism and antithyroid-induced immunological reactions.
  
  
  CONCLUSIONS
  The E-state approach provides guidelines to economize efforts and cost of designing new antithyroid drugs.
authors.affiliation: College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
authors.forename: R R
authors.initials: RR
authors.lastname: Abou-Shaaban
authors.forename: H A
authors.initials: HA
authors.lastname: al-Khamees
authors.forename: H S
authors.initials: HS
authors.lastname: Abou-Auda
authors.forename: A P
authors.initials: AP
authors.lastname: Simonelli
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013956:Antithyroid Agents / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004563:Electrochemistry; D007455:Iodine / Q000737:chemistry*; D007928:Lethal Dose 50; D008163:Luminescent Measurements; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D013890:Thiourea / Q000737:chemistry*
chemical_list: D000975:Antioxidants; D013956:Antithyroid Agents; D007455:Iodine; D013890:Thiourea