title: Design and synthesis of novel flexible ester-containing analogs of tamoxifen and their evaluation as anticancer agents.
abstract: BACKGROUND
  Tamoxifen (TAM) is metabolized to the more active 4-hydroxytamoxifen by CYP2D6 enzyme. Due to the genetic polymorphisms in CYP2D6, clinical outcomes of TAM treatment vary. Novel flexible TAM analogs with altered activation pathway were synthesized and were tested for their antiproliferative action on MCF-7 cell lines and their binding affinity for ERα and ERβ.
  
  
  RESULTS
  All compounds showed better antiproliferative activity than TAM. Compound 3 showed 80-times more ERα binding than TAM, 900-times more selectivity toward ERα. Compound 3 was tested on the entire National Cancer Institute cancerous cell lines; results indicated a broad spectrum anticancer activity.
  
  
  CONCLUSIONS
  The novel analogs were more potent than TAM with higher selectivity toward ERα and with potential metabolic stability toward CYP2D6.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, 11835 Cairo, Egypt.
authors.forename: Nehal H
authors.initials: NH
authors.lastname: Elghazawy
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Department Drug Development and Optimization (DDOP)Campus, C2.3Saarland UniversityD-66123 Saarbrücken.
authors.forename: Mathias
authors.initials: M
authors.lastname: Engel
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Department Drug Development and Optimization (DDOP)Campus, C2.3Saarland UniversityD-66123 Saarbrücken.
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
authors.affiliation: Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) Department Drug Development and Optimization (DDOP)Campus, C2.3Saarland UniversityD-66123 Saarbrücken.
authors.forename: Mostafa M
authors.initials: MM
authors.lastname: Hamed
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, 11835 Cairo, Egypt.
authors.forename: Nermin S
authors.initials: NS
authors.lastname: Ahmed
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy & Biotechnology, German University in Cairo, 11835 Cairo, Egypt.
authors.forename: Ashraf H
authors.initials: AH
authors.lastname: Abadi
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004952:Esters; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D013629:Tamoxifen
keywords: CYP2D6; MCF7; McMurry; SERM; allelic variation; breast cancer; esterases; metabolism; personalized medicine; tamoxifen