title: In vitro evaluation of 3-arylcoumarin derivatives in A549 cell line.
abstract: Coumarins are naturally-occurring compounds with diverse and interesting biological activities. In the present study, we evaluated the in vitro cytotoxic effect of 8-(acetyloxy)-3-[4-(acetyloxy)phenyl]-2-oxo-2H-chromen-7-yl acetate (6); 8-(acetyloxy)-3-(4-methanesulfonyl phenyl)-2-oxo-2H-chromen-7-yl acetate (7); 4-(2-oxo-2H-chromen-3-yl)phenyl acetate (8); 3-(4-methanesulfonylphenyl)-2H-chromen-2-one (9); 4-(4-methyl-2-oxo-2H-chromen-3-yl)phenyl acetate (10); 3-(4-methanesulfonylphenyl)-4-methyl-2H-chromen-2-one (11); 8-(acetyloxy)-3-[4-(acetyloxy)phenyl]-4-methyl-2-oxo-2H-chromen-7-yl acetate (12); and 5-(acetyloxy)-3-[4-(acetyloxy) phenyl]-2-oxo-2H-chromen-7-yl acetate (13) in human lung (A549) cancer and normal lung (MRC-9) cell lines at different concentrations for 48 h using crystal violet dye binding assay. The cytotoxic effect of these coumarin derivatives were compared to the standard drug, docetaxel. Furthermore, the effect of the most active compound on the cell-cycle using propidium iodide, mitochondrial membrane potential (MMP) using tetramethyl rhodamine methyl ester (rhodamine-123) and reactive oxygen species (ROS) production using 2',7'-dichlorofluorescin diacetate (PCFDA) were also evaluated.
  
  
  RESULTS
  Compound 7: had the greatest cytotoxic effect (cytotoxic concentration, CC50=24 μM) and selectivity (MRC-9; CC50>100 μM; inactive) in the A549 cell line, and caused cells to arrest in the S phase of the cell cycle, loss of MMP and increased ROS production in a concentration-dependent manner.
  
  
  CONCLUSIONS
  These findings suggest that compound 7: could serve as a new lead for the development of novel synthetic compounds with enhanced anticancer activity.
authors: Department of Chemistry, Florida A and M University, Tallahassee, FL, U.S.A. musiliyu.musa@famu.edu.
authors: Musiliyu A
authors: MA
authors: Musa
authors: Department of Biological Sciences, Florida A and M University, Tallahassee, FL, U.S.A.
authors: Moise Y
authors: MY
authors: Joseph
authors: Department of Biological Sciences, Florida A and M University, Tallahassee, FL, U.S.A.
authors: Lekan M
authors: LM
authors: Latinwo
authors: Department of Biological Sciences, Florida A and M University, Tallahassee, FL, U.S.A.
authors: Veera
authors: V
authors: Badisa
authors: College of Pharmacy and Pharmaceutical Sciences, Florida A and M University, Tallahassee, FL, U.S.A.
authors: John S
authors: JS
authors: Cooperwood
mesh_terms: D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D006801:Humans; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D003374:Coumarins; D017382:Reactive Oxygen Species; D020782:Matrix Metalloproteinases
keywords: 3-Arylcoumarin derivatives; cell cycle phase; cytotoxic effect; mitochondrial transmembrane potential; reactive oxygen species production