title: Synthesis and Evaluation of A New Series of Thiazole Derivatives as Potential Antitumor Agents and MMP Inhibitors.
abstract: BACKGROUND
  In recent years, the relationship between overexpression of matrix metalloproteinases (MMPs) and tumor invasion/metastasis has prompted researchers to develop MMP inhibitors as anticancer drugs.
  
  
  OBJECTIVE
  The aim of this study was to design and synthesize new thiazole-based anticancer agents targeting MMPs.
  
  
  METHODS
  New thiazole derivatives were synthesized and investigated for their cytotoxic effects on A549 human lung adenocarcinoma, MCF-7 human breast adenocarcinoma and NIH/3T3 mouse embryonic fibroblast cell lines using MTT assay. The potential inhibitory effects of the best candidates on gelatinases (MMP-2, MMP-9), and collagenases (MMP-1, MMP-8, MMP-13) were evaluated.
  
  
  RESULTS
  Ethyl 2-[2-((4-amino-5-(phenoxymethyl)-4H-1,2,4-triazol-3-yl)thio)acetamido]-4-methylthiazole-5-carboxylate (3) was found to be the most promising anticancer agent against MCF-7 cell line due to its selective inhibitory effect on MCF-7 cells with an IC50 value of 20.6±0.3 μg/mL when compared with cisplatin (IC50= 35.31±0.51 μg/mL). Compound 3 also showed multiple MMP (MMP-1, MMP-8 and MMP-9) inhibitory activity (10.56±1.70, 20 and 7.28±1.49%, respectively).
  
  
  CONCLUSIONS
  The notable anticancer activity and selectivity of compound 3 on MCF-7 cell line can be attributed to multiple MMP inhibition potential.
authors: Zafer Asim
authors: ZA
authors: Kaplancikli
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Mehlika Dilek
authors: MD
authors: Altıntop
authors: Ozlem
authors: O
authors: Atli
authors: Belgin
authors: B
authors: Sever
authors: Merve
authors: M
authors: Baysal
authors: Halide Edip
authors: HE
authors: Temel
authors: Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey.
authors: Fatih
authors: F
authors: Demirci
authors: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
authors: Ahmet
authors: A
authors: Ozdemir
mesh_terms: D000818:Animals; 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; D061965:Matrix Metalloproteinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D051379:Mice; D015394:Molecular Structure; D041681:NIH 3T3 Cells; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D061965:Matrix Metalloproteinase Inhibitors; D013844:Thiazoles; D020782:Matrix Metalloproteinases
keywords: Thiazole; anticancer activity; matrix metalloproteinase; oxadiazole; triazole