title: Hologram quantitative structure-activity relationship and comparative molecular interaction field analysis of aminothiazole and thiazolesulfonamide as reversible LSD1 inhibitors.
abstract: BACKGROUND
  LSD-1 is an enzyme that removes methyl groups from lysine residues of histone proteins. LSD-1 inhibition decreases cellular proliferation and therefore represents a therapeutic target for cancer treatment. MAO and LSD-1 are both flavin adenine dinucleotide-dependent MAOs, and the MAO inhibitor, tranylcypromine, is currently undergoing clinical trials for cancer treatment because it acts as an irreversible LSD-1 inhibitor.
  
  
  METHODS
  The present study investigated new reversible LSD-1 inhibitors, in order to develop novel selective anticancer agents. We constructed 2 and 3D quantitative structure-activity relationship models by using a series of 54 aminothiazole and thiazolesulfonamide derivatives.
  
  
  RESULTS
  The models were validated internally and externally (q(2) , 0.691 and 0.701; r(2) , 0.894 and 0.937; r(2) test , 0.785 and 0.644, for 2 and 3D models, respectively). Fragment contribution maps, as well as steric and electrostatic contour maps were generated in order to obtain chemical information related to LSD-1 inhibition.
  
  
  CONCLUSIONS
  The thiazolesulfonamide group was fundamental to the inhibition of LSD-1 by these compounds and that bulky and aromatic substituents at the thiazole ring were important for their steric and electrostatic interactions with the active site of LSD-1.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Vinícius G
authors.initials: VG
authors.lastname: Maltarollo
authors.affiliation: School of Arts, Sciences & Humanities, University of São Paulo, São Paulo, Brazil.|Center of Natural & Human Sciences, Federal University of ABC, Santo André, São Paulo, Brazil.
authors.forename: Káthia M
authors.initials: KM
authors.lastname: Honório
authors.affiliation: Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ri-beirão Preto, São Paulo, Brazil.
authors.forename: Flavio S
authors.initials: FS
authors.lastname: Emery
authors.affiliation: School of Pharmacy, University of East Anglia, Norwich, UK.
authors.forename: Arasu
authors.initials: A
authors.lastname: Ganesan
authors.affiliation: Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Gustavo H G
authors.initials: GH
authors.lastname: Trossini
mesh_terms: D055808:Drug Discovery; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D056466:Histone Demethylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D013449:Sulfonamides; D013844:Thiazoles; C004483:2-aminothiazole; D056466:Histone Demethylases; C495195:KDM1A protein, human