Divya, Rajan (2016) Molecular Modelling, Synthesis and Evaluation of Pyridazine Derivatives as Potent Anti-Cancer Agents. Masters thesis, KMCH College of Pharmacy, Coimbatore.
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Abstract
The present study was designed to synthesize and investigate the cytotoxic and therapeutic effects of Pyrazolo benzpyridazine derivatives against DMH induced colon carcinoma in Sprague Dawley(SD) Rats. Docking studies were performed with VEGFR2 in order to understand the interaction of ligand with targeted receptor. Based on docking scores and chemical availability, 6 compounds were synthesised and confirmed through spectral analytical techniques (UV, IR, NMR and MASS). DPPH and ABTS antioxidant activity were performed in synthesised compounds and they showed good antioxidant activity. They were screened against Human Colon Cancer (HT29) cell line. Out of these, Pz-5 was found to be potent with promising IC50 Value of 27.64 μM against HT29 cell line. From the acute toxicity studies conducted on Female Wistar rats, the compound PZ-5 showed to be safe upto the dose of 2000mg/kg. Further in vivo studies was carried out for PZ-5 by inducing the colon carcinoma with the chemical carcinogen DMH(20mg/kg) for 4months in SD Rats and therapeutic effect of the compound PZ-5 on various haematological and enzymatic parameters were studied by treating with two dose levels (100mg/kg,200mg/kg) for 30days. The compound PZ-5 moderately increased the in vivo antioxidant levels like Reduced Glutathione (GSH), Glutathione peroxidise (GPx), Catalase (CAT), Super oxide dismutase (SOD), and Total protein, and reduced the lipid peroxidation in a dose dependent manner. The blood cell count, serum ALP, TCA cycle enzyme succinate dehydrogenase levels were also moderately altered on treatment with the compound at a dose of 200mg/kg as compared with negative control group in a dose dependent manner. These results suggested that the compound has a significant cytotoxic activity against colon cancer.
| Item Type: | Thesis (Masters) |
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| Uncontrolled Keywords: | Molecular Modelling ; Synthesis ; Pyridazine Derivatives ; Potent Anti-Cancer Agents |
| Subjects: | PHARMACY > Pharmacology |
| Depositing User: | Ravindran C |
| Date Deposited: | 05 Jan 2018 05:46 |
| Last Modified: | 05 Jan 2018 08:16 |
| URI: | http://repository-tnmgrmu.ac.in/id/eprint/4959 |
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