title: Cytogenetic and antineoplastic effects of modified steroidal alkylators.
abstract: BACKGROUND
  The aim of this study was to design new potentially antineoplastic agents by combining nitrogen mustard with steroidal skeleton, in an effort to improve specificity and simultaneously to reduce systemic toxicity. The steroidal part is aimed to act as a biological platform enabling the alkylating moiety to approach its site of action by altering its physicochemical properties.
  
  
  METHODS
  The compounds tested have, as alkylating agents, either p-N,N-bis(2-chloroethyl)aminophenyl-butyrate or p-N,N-bis(2-chloroethyl)aminophenyl-acetate esterified with a modified steroidal nucleus. The four newly synthesized compounds were compared on a molar basis, regarding their ability to induce sister chromatid exchanges and modify proliferation rate indices in cultured human lymphocytes. Life span of BDF1 mice inoculated with L1210 leukemia was also estimated (antileukemic activity).
  
  
  RESULTS
  A compound having p-N,N-bis(2-chloroethyl)aminophenyl-acetate as the alkylator and two ketone groups in the steroidal part demonstrated the highest statistically significant enhancement of sister chromatid exchanges and suppression of proliferation rate indices, and also caused significant antineoplastic activity. The other compounds proved less active.
  
  
  CONCLUSIONS
  These results suggest that cytogenetic and antileukemic activity of alkylating steroidal esters depends on the configuration of the whole molecule and the appropriate combination of the alkylator with the steroidal molecule.
authors.affiliation: Laboratory of Biology and Genetics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: Irini
authors.initials: I
authors.lastname: Karapidaki
authors.forename: Athanasios
authors.initials: A
authors.lastname: Papageorgiou
authors.forename: George
authors.initials: G
authors.lastname: Geromichalos
authors.forename: Manolis
authors.initials: M
authors.lastname: Fousteris
authors.forename: Ioanna
authors.initials: I
authors.lastname: Papaconstadinou
authors.forename: George
authors.initials: G
authors.lastname: Pairas
authors.forename: Anna
authors.initials: A
authors.lastname: Koutsourea
authors.forename: Denis
authors.initials: D
authors.lastname: Mourelatos
authors.forename: Sotiris
authors.initials: S
authors.lastname: Nikolaropoulos
authors.forename: Theodoros
authors.initials: T
authors.lastname: Lialiaris
mesh_terms: D000731:Androstanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D007939:Leukemia L1210 / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D012854:Sister Chromatid Exchange / Q000187:drug effects
chemical_list: D000731:Androstanes; D018906:Antineoplastic Agents, Alkylating