title: Synthesis and Evaluation of Some Dibromoquinazoline-sulphonamide Hybrids and some Schiff´s Base Analogs for their Cytotoxic Activity.
abstract: BACKGROUND
  Cancer is one of the most dangerous diseases with quite a high mortality rate. Many quinazoline derivatives show potent anticancer activity.
  
  
  OBJECTIVE
  In this work our aim is to develop novel, safe and effective anticancer agents.
  
  
  METHODS
  New 6,8-dibromo-2-(4-chlorophenyl)-quinazoline-sulphonamide hybrids and some Schiff´s base analogs were synthesized, and their structures were confirmed by spectral and elemental analysis. Cytotoxicity of all synthesized compounds was evaluated on three cancer cell lines MCF7, HCT116 and HEPG2 using sulpharodamine- B assay method and doxorubicin as a reference drug. All tested compounds show promising cytotoxic activities on the three cell lines.
  
  
  RESULTS
  Compound IXd was 2 times more active than doxorubicin on MCF7 cancer cells, while it was 3 times more potent than doxorubicin on HCT116 cancer cells. Compound IV was 2 times more active than doxorubicin while compound VI exhibited similar activity to doxorubicin on HEPG2 cell line. The most active compounds were tested against epidermal growth factor receptor tyrosine kinase (EGFR TK). Compounds IV, IXd, IXf show the most potent inhibitory percent 62.3, 91.1, 91.6 respectively. Compounds IV, V, VII, IXd, IXf caused a significant increase of CASP3 activity with range 86.5-37.6 %.
  
  
  CONCLUSIONS
  The present work led to the discovery of new cytotoxic compounds having quinazoline pharmacophore.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.|Research Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Marwa F
authors.initials: MF
authors.lastname: Ahmed
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz 71468-64685, Iran.
authors.forename: Radwan
authors.initials: R
authors.lastname: El-Haggar
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D012545:Schiff Bases; D013449:Sulfonamides
keywords: Quinazolinone-sulphonamide hybrids; analogs; antitumor; cytotoxic activity.; schiff´s base; tyrosine kinases