title: Cytogenetic activity of newly synthesized 1,5-benzodiazepines in normal human lymphocyte cultures.
abstract: BACKGROUND
  Many different types of benzodiazepine medications exist to treat a wide array of psychological and physical diseases based on dosage and implications. Benzodiazepines are generally considered as safe and effective drugs in short term; however, cognitive impairments and paradoxical effects occasionally occur. Our recent studies have shown that some 1,4-benzodiazepines exhibit cytogenetic activity (alprazolam, diazepam, and lorazepam) in normal human lymphocyte cultures. 1,5-Benzodiazepine derivatives are used in the synthesis of fused ring compounds, to study the chemical structure-pharmacological activity correlation. We synthesized four compounds of this category with small structural differences.
  
  
  OBJECTIVE
  The aim of this study was to investigate their cytogenetic activity in vitro at doses equivalent to the per os doses of the used 1,4-benzodiazepines. Sister chromatid exchanges (SCEs), proliferation rate index, and mitotic index were evaluated in lymphocytes of peripheral blood cultures from two healthy donors.
  
  
  RESULTS
  Three of the newly synthesized compounds exhibited positive cytogenetic activity (statistically significant reduction of SCEs, p < 0.01, t-test), without showing cytostatic properties.
  
  
  CONCLUSIONS
  The observed reduction of the lymphocytes' SCEs because of 1,5-benzodiazepines' activity is remarkable and requires further investigation to improve pharmacological effects.
authors.affiliation: Laboratory of General Biology and Genetics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Ekonomopoulou
authors.forename: Constantinos A
authors.initials: CA
authors.lastname: Tsoleridis
authors.forename: Maria
authors.initials: M
authors.lastname: Argyraki
authors.forename: Eleni
authors.initials: E
authors.lastname: Polatoglou
authors.forename: Julia
authors.initials: J
authors.lastname: Stephanidou-Stephanatou
authors.forename: Zafiroula
authors.initials: Z
authors.lastname: Iakovidou-Kritsi
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001569:Benzodiazepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D020732:Cytogenetic Analysis; D003975:Diazepam / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008140:Lorazepam / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008940:Mitotic Index; D012854:Sister Chromatid Exchange / Q000187:drug effects*
chemical_list: D001569:Benzodiazepines; D008140:Lorazepam; D003975:Diazepam; D000525:Alprazolam