title: Design, synthesis, docking study and cytotoxic activity evaluation of some novel letrozole analogs.
abstract: BACKGROUND
  Breast cancer is the most common type of female cancer. One class of hormonal therapy for breast cancer drugs -non steroidal aromatase inhibitors- are triazole analogues. In this work, some derivatives of these drugs was designed and synthesized. All synthesized compounds were evaluated for their cytotoxic activities on breast cancer cell lines (MDA-MB-231, T47D and MCF-7).
  
  
  METHODS
  Our synthetic route for designed compounds started from 4-bromotolunitrile which was reacted with 1H-1,2,4-triazole to afford 4-(4-cyanobenzyl)-1,2,4-triazole. The reaction of later compound with aromatic aldehydes led to formation of the designed compounds. Eleven novel derivatives 1a-k were tested for their cytotoxic activities on three human breast cancer cell lines.
  
  
  RESULTS
  Among the synthesized compound, 4-[2-(3-chlorophenyl)-1-(1H-1,2,4-triazol-1-yl)ethenyl]benzonitrile (1c) showed the highest activity against MCF-7 and MDA-MB-231 cell lines and 4-[2-(4-methoxyphenyl)-1-(1H-1,2,4-triazol-1-yl)ethenyl]benzonitrile (1 h) exhibited highest activity against T47D cell line. According to cytotoxic activities results, compound 4-[2-(4-dimethylamino)-1-(1H-1,2,4-triazol-1-yl)ethenyl]benzonitrile (1 k) showed comparative activity against T47D and MDA-MB-231 cell lines with compound (1 h) and our reference drug Etoposide.
  
  
  CONCLUSIONS
  In the process of anti-cancer drug discovery, to find new potential anti-breast cancer agents, we designed and synthesized a novel series of letrozole analogs. Cytotoxicity evaluation revealed that compounds (1c) and (1 k) were the most potent compounds with comparative activity with Etoposide. The results revealed that π-π interactions are responsible for the enzyme inhibitions of compounds (1 c) and (1 k).
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. vosoghim@tums.ac.ir.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Vosooghi
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. Firoozpour@gmail.com.
authors.forename: Loghman
authors.initials: L
authors.lastname: Firoozpour
authors.affiliation: Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran. r_rodaki@yahoo.com.
authors.forename: Abolfazl
authors.initials: A
authors.lastname: Rodaki
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, Tehran, Iran. pordeli@ibb.ut.ac.ir.
authors.forename: Mahboobeh
authors.initials: M
authors.lastname: Pordeli
authors.affiliation: Department of Biotechnology, Iranian Research Organization for Science and Technology, Tehran, Iran. safavi_maliheh@yahoo.com.
authors.forename: Maliheh
authors.initials: M
authors.lastname: Safavi
authors.affiliation: Institute of Biochemistry and Biophysics, University of Tehran, PO Box 13145-1384, Tehran, Iran. ardestany@ut.ac.ir.
authors.forename: Sussan K
authors.initials: SK
authors.lastname: Ardestani
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran. a.dadgar@gmail.com.
authors.forename: Armin
authors.initials: A
authors.lastname: Dadgar
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran. aliasadipour@yahoo.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Asadipour
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran. moshafi14@yahoo.com.
authors.forename: Mohammad Hassan
authors.initials: MH
authors.lastname: Moshafi
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medicinal Sciences, Kerman, Iran. aforoumadi@yahoo.com.|Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran. aforoumadi@yahoo.com.
authors.forename: Alireza
authors.initials: A
authors.lastname: Foroumadi
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis* / Q000494:pharmacology*; D047072:Aromatase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017076:Computer-Aided Design; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D000077289:Letrozole; D061986:MCF-7 Cells; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047072:Aromatase Inhibitors; D009570:Nitriles; D014230:Triazoles; D000077289:Letrozole