title: Phthalimide analogs as probable 15-lipoxygenase-1 inhibitors: synthesis, biological evaluation and docking studies.
abstract: BACKGROUND
  Recent studies have been explained the role of lipoxygenases (LOX) in the origin of cancer. Among the lipoxygenases, the 5-LOX, 12-LOX and 15-LOX are more important in the cause of neoplastic disorders. In the present investigation, a new series of anticancer agents with 1,3,4-thiadiazole and phthalimide substructures were synthesized and their in vitro cytotoxicity was evaluated by MTT assay. Moreover, enzyme inhibitory potency was also assessed by enzymatic protocol towards 15-LOX-1. Molecular docking was performed to explore in silico binding mode of the target compounds.
  
  
  RESULTS
  Tested compounds showed a better cytotoxic activity against HT29 cell line (colorectal cancer) in comparison with other cell lines (PC3: prostate carcinoma; SKNMC: neuroblastoma). Unfortunately, all of the tested derivatives rendered lower inhibitory potency than quercetin towards 15-LOX-1. Four hydrogen bonds were detected in docking studies for compound 4d as the most potent derivative in enzymatic assay.
  
  
  CONCLUSIONS
  The biological results of reported compounds in this research were not so satisfactory. But, further structural modifications are necessary to improve the bioactivity of these derivatives.
authors.affiliation: Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. aliabadi.alireza@gmail.com.|Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. aliabadi.alireza@gmail.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Aliabadi
authors.affiliation: Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. amohammadifa@kums.ac.ir.|Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. amohammadifa@kums.ac.ir.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mohammadi-Farani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. zhos@yahoo.com.|Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran. zhos@yahoo.com.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Hosseinzadeh
authors.affiliation: Neurobiomedical Research Center, Yazd Shahid Sadoughi University of Medical Sciences, Yazd, Iran. hnaderof@gmail.com.
authors.forename: Hamid
authors.initials: H
authors.lastname: Nadri
authors.affiliation: Neurobiomedical Research Center, Yazd Shahid Sadoughi University of Medical Sciences, Yazd, Iran. alirezampr@gmail.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Pharmaceutical Sciences Research Center, School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. frahmadi@gmail.com.|Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran. frahmadi@gmail.com.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Ahmadi
mesh_terms: D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D016859:Lipoxygenase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D010797:Phthalimides / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; D010797:Phthalimides; C515716:ALOX15 protein, human; D001093:Arachidonate 15-Lipoxygenase