title: Anticancer Activities of New N-hetaryl-2-cyanoacetamide Derivatives Incorporating 4,5,6,7-Tetrahydrobenzo[b]thiophene Moiety.
abstract: OBJECTIVE
  Novel series of N-(4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives are synthesized.
  
  
  METHODS
  The structure of these compounds was elucidated using different spectral tools. Compounds were evaluated for their cytotoxic activities against different types of human cancer cell lines including, breast (MCF-7, T47D, MDA MB231); liver (HEPG-2); colon (HCT116); prostate (PC3); and cervix (HELA) cells. In this study, we used compounds 11 and 12 that showed the highest cytotoxicity on PC3 and HEPG2 cells, to explore their effects on apoptosis, metastasis and angiogenesis of cancer cells.
  
  
  RESULTS
  Results revealed that the growth inhibition produced by the two selected compounds was due to cytocidal and not due to cytostatic effect in both cell lines. This cytocidal effect was due to up-regulation of caspases-3, and- 9. In addition, the two compounds inhibited the expression of metalloproteinases-2 and 9 (MMP 2&9). Moreover, HIF-1alpha and VEGF expressions were inhibited by both compounds.
  
  
  CONCLUSIONS
  In conclusion, N-(4, 5, 6, 7-tetrahydrobenzo[b]thiophen-2-yl) cyanoacetamide derivatives showed different anticancer potential against different cancer cell lines. Compounds 11 and 12 showed the most active cytotoxicity against PC3 and HepG2 cells. Both compounds have apoptotic, anti- metastatic and anti-angiogenic effects.
authors.affiliation: Department of Chemistry (Biochemistry Branch), Faculty of Science, Cairo University, Giza, Egypt.
authors.forename: Magda F
authors.initials: MF
authors.lastname: Mohamed
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Yasmin M
authors.initials: YM
authors.lastname: Attia
authors.affiliation: Department of Cancer Biology, National Cancer Institute, Cairo University, Giza, Egypt.
authors.forename: Samia A
authors.initials: SA
authors.lastname: Shouman
authors.affiliation: Department of Chemistry, Faculty of Science, Cairo University, 12613 Giza, A. R, Egypt.
authors.forename: Ismail A
authors.initials: IA
authors.lastname: Abdelhamid
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D009570:Nitriles; D013876:Thiophenes; C031594:2-cyanoacetamide
keywords: 5; 6; 7-tetrahydrobenzo[b]thiophen-2-yl)cyanoacetamide; Cytotoxicity; HIF-
  1alpha; Metalloproteinase; N-(4; VEGF; caspases; in vitro screening