Chemopreventive potential of 3-[2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino]-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz[a]anthracene (DMBA) induced hamster buccal pouch carcinogenesis.
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.
Thanusu
J
J
Synthetic Organic Chemistry Laboratory, Department of Chemistry, Faculty of Science, Annamalai University, Annamalai Nagar, Tamil Nadu, India.
Kanagarajan
V
V
Nagini
S
S
Gopalakrishnan
M
M
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000633:toxicity; D000818:Animals; D000873:Anthracenes / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008647:Mesocricetus; D015394:Molecular Structure; D009061:Mouth Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D010881:Piperidones / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D011897:Random Allocation; D013867:Thiohydantoins / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D047368:Tumor Burden / Q000187:drug effects; D005723:gamma-Glutamyltransferase / Q000378:metabolism
C556780:3-(2,6-bis(4-fluorophenyl)-3-methylpiperidin-4-ylideneamino)-2-thioxoimidazolidin-4-one on 7,12-dimethylbenz(a)anthracene; D000873:Anthracenes; D016588:Anticarcinogenic Agents; D015415:Biomarkers; D002273:Carcinogens; D010880:Piperidines; D010881:Piperidones; D013867:Thiohydantoins; D015127:9,10-Dimethyl-1,2-benzanthracene; D005979:Glutathione Peroxidase; D005723:gamma-Glutamyltransferase; D005982:Glutathione Transferase; D005978:Glutathione