Synthetic Organic Chemistry Laboratory, Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
J Enzyme Inhib Med Chem. 2010 Dec;25(6):836-43. doi: 10.3109/14756361003724786. Epub 2010 Apr 7.
In the present work, a new bis heterocyclic compound comprising both the piperidone and thiohydantoin nuclei namely 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one was synthesised and characterised with the help of mp, elemental analysis, FT-IR, MS and one-dimensional NMR ((1)H and (13)C) spectra. The inhibitory effect of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz[a]anthracene (DMBA) induced buccal pouch carcinogenesis was investigated in Syrian male hamsters. All the hamsters that were painted with DMBA on their buccal pouches for 14 weeks developed squamous cell carcinoma. Administration of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one effectively suppressed the oral carcinogenesis initiated with the DMBA as revealed by a reduced incidence of neoplasms. Lipid peroxidation, glutathione (GSH) content and the activities of glutathione peroxidase (GPx), glutathione S-transferase (GST) were used to biomonitor the chemopreventive potential of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one. Lipid peroxidation was found to be significantly decreased, whereas GSH, GPx, GST and GGT were elevated in the oral mucosa of tumour bearing animals. Our data suggest that 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one may exert its chemopreventive effects in the oral mucosa by modulation of lipid peroxidation, antioxidants and detoxification systems.
在本工作中，合成了一种新的双杂环化合物，它包含哌啶酮和硫代海因核，即 3-[2,6-双(4-氟苯基)-3-甲基哌啶-4-亚基氨基]-2-硫代咪唑烷-4-酮，并借助熔点、元素分析、FT-IR、MS 和一维 NMR((1)H 和 (13)C)谱进行了表征。研究了 3-[2,6-双(4-氟苯基)-3-甲基哌啶-4-亚基氨基]-2-硫代咪唑烷-4-酮对 7,12-二甲基苯并[a]蒽（DMBA）诱导的颊囊癌变的抑制作用。所有在颊囊中涂抹 DMBA 14 周的叙利亚雄性仓鼠均发展为鳞状细胞癌。用 DMBA 诱导口腔癌发生后，给予 3-[2,6-双(4-氟苯基)-3-甲基哌啶-4-亚基氨基]-2-硫代咪唑烷-4-酮可有效抑制肿瘤的发生，肿瘤发生率降低。脂质过氧化、谷胱甘肽（GSH）含量以及谷胱甘肽过氧化物酶（GPx）、谷胱甘肽 S-转移酶（GST）的活性用于监测 3-[2,6-双(4-氟苯基)-3-甲基哌啶-4-亚基氨基]-2-硫代咪唑烷-4-酮的化学预防潜力。发现脂质过氧化明显降低，而肿瘤动物口腔黏膜中的 GSH、GPx、GST 和 GGT 升高。我们的数据表明，3-[2,6-双(4-氟苯基)-3-甲基哌啶-4-亚基氨基]-2-硫代咪唑烷-4-酮可能通过调节脂质过氧化、抗氧化剂和解毒系统在口腔黏膜中发挥其化学预防作用。
