title: Characterization of novel synthesized small molecular compounds against non-small cell lung cancer.
abstract: BACKGROUND
  With the exception of surgery, the standard platinum-based chemotherapeutic agents are the preferred treatment for non-small cell lung cancer (NSCLC); however little improvement (5-year survival) has been made. Therefore it is highly desirable to develop innovative therapeutic agents for NSCLC treatment.
  
  
  METHODS
  Highly enantioselective synthetic methods were developed and a broad compound library was established. Cell toxicity, cell sensitivity, cell proliferation, cell invasion, and three-dimensional colony formation assays were used to assess the anticancer potential of these compounds in non-small-cell lung cancer (NSCLC) cell lines.
  
  
  RESULTS
  We found that the S-form of compound PL54 (PL54S, 5-20 μM) exhibited strong anticancer activity in 5 tested NSCLC cell lines. We further synthesized a highly pure R-form enantiomer of PL54 (PL54R) and its racemate (PL54Rac) and characterized their anticancer activities. The results showed that PL54S is more potent than PL54R and PL54Rac against the tested cell lines. Furthermore, less cellular toxicity was observed in the normal human lung fibroblasts. Similarly, PL54S displayed greater anti-colony formation activity compared with PL54R and PL54Rac. The cellular sensitivity assay revealed that PL54S and PL54Rac significantly suppressed cologenic formation compared with PL54R and dimethyl sulfoxide controls (p<0.01). All PL54 compounds (5 to 20 μM) significantly inhibited cell proliferation and invasion of the A549 cell line (p<0.01). A soft agar colony formation assay revealed that PL54S and PL54Rac (10 mM), but not PL54R, significantly inhibited colony formation of tested NSCLC cells (p<0.01).
  
  
  CONCLUSIONS
  The stereospecific compounds may prove to be a novel technique for the treatment of NSCLC.
authors.affiliation: Division of Thoracic and Cardiovascular Surgery, Department of Surgery, University of Virginia, Charlottesville, Virginia 22908-0679, USA.
authors.forename: Yunge
authors.initials: Y
authors.lastname: Zhao
authors.forename: Mark
authors.initials: M
authors.lastname: Turlington
authors.forename: Damien J
authors.initials: DJ
authors.lastname: LaPar
authors.forename: David R
authors.initials: DR
authors.lastname: Jones
authors.forename: David A
authors.initials: DA
authors.lastname: Harris
authors.forename: Irving L
authors.initials: IL
authors.lastname: Kron
authors.forename: Lin
authors.initials: L
authors.lastname: Pu
authors.forename: Christine L
authors.initials: CL
authors.lastname: Lau
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds