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2-取代苯并噻唑衍生物的合成及其对胰腺癌细胞的抗癌作用和抗氧化活性

Synthesis of 2-Substituted Benzothiazole Derivatives and Their Anticancer Effects and Antioxidant Activities Against Pancreatic Cancer Cells.

作者信息

Uremis Nuray, Uremis Muhammed Mehdi, Tolun Fatma Inanc, Ceylan Mustafa, Doganer Adem, Kurt Akif Hakan

机构信息

Department of Medical Biochemistry, Faculty of Medicine, Kahramanmaras Sutcu Imam University, Kahramanmaras, Turkey.

Department of Chemistry, Faculty of Science and Letters, Gaziosmanpasa University, Tokat, Turkey.

出版信息

Anticancer Res. 2017 Nov;37(11):6381-6389. doi: 10.21873/anticanres.12091.

DOI:10.21873/anticanres.12091
PMID:29061823
Abstract

Pancreatic cancer is one of the deadliest malignancies characterized by strong resistance to almost all chemotherapeutic agents and radiotherapy. In this study, we aimed to investigate the anticancer effect, enzymatic antioxidant activity [superoxide dismutase (SOD), glutathione peroxidase (GPx)] and total antioxidant capacity (TAC) of synthesized benzothiazole compounds against adenocarcinoma cancer cells (PANC-1). 2-((1S,2S)-2-((E)-4-nitrostyryl)cyclopent-3-en-1-yl)benzo[d]thiazole and 2-((1S,2S)-2-((E)-4-fluorostyryl) cyclopent-3-en-1-yl)benzo[d]thiazole containing 2-substituted benzothiazole group were synthesized in two steps. PANC-1 cells were treated with different concentrations of benzothiazole compounds (5, 25, 50. 75 and 100 μM) for 48 h and their cytotoxicity effects were determined by the MTT assay. To determine whether these compounds induced apoptosis, PANC-1 cells were treated with increasing concentrations of the synthetic products. Our study showed that the synthesized compounds have antiproliferative effects against PANC-1 cells and reduced cell viability. These compounds induced apoptosis of pancreatic cancer cells and at the same time reduced the activity of SOD and GPx and reduced TAC. On the basis of these findings, these synthesized benzothiazole compounds may be considered as a potential therapeutic drug against human PANC-1 cancer cells.

摘要

胰腺癌是最致命的恶性肿瘤之一,其特点是对几乎所有化疗药物和放疗都具有很强的抗性。在本研究中,我们旨在研究合成的苯并噻唑化合物对胰腺腺癌细胞(PANC-1)的抗癌作用、酶促抗氧化活性[超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPx)]和总抗氧化能力(TAC)。含2-取代苯并噻唑基团的2-((1S,2S)-2-((E)-4-硝基苯乙烯基)环戊-3-烯-1-基)苯并[d]噻唑和2-((1S,2S)-2-((E)-4-氟苯乙烯基)环戊-3-烯-1-基)苯并[d]噻唑通过两步合成。用不同浓度(5、25、50、75和100μM)的苯并噻唑化合物处理PANC-1细胞48小时,并通过MTT法测定其细胞毒性作用。为了确定这些化合物是否诱导细胞凋亡,用浓度递增的合成产物处理PANC-1细胞。我们的研究表明,合成的化合物对PANC-1细胞具有抗增殖作用并降低细胞活力。这些化合物诱导胰腺癌细胞凋亡,同时降低SOD和GPx的活性并降低TAC。基于这些发现,这些合成的苯并噻唑化合物可被视为针对人PANC-1癌细胞的潜在治疗药物。

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