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Title: Association of Phosphoinositide 3 Kinase mediated signaling inhibition by Quinoxaline synthetic and Meroterpenoid natural derivatives with Cancer cell death
Researcher: Asif Khurshid
Guide(s): Dar, Abid Hamid, Shakir Ali
University: Jamia Hamdard University
Completed Date: 2015
Abstract: In the present study, an approach was intended at the inhibition of target signaling molecules that may be precisely involved in the commencement and advancement of colorectal carcinoma between several types of newlineother malignancies. Consequently, the study defines to the ground of therapeutics, predominantly to the orientation of target facilitated apoptosis thereof cytotoxicity newlineand anti-tumor activity exhibited by small molecules based on Quinazoline and newlineMeroterpenoid scaffolds i.e. 7, 8, 9, 10-Tetrahydroazepino [2, 1- b] quinazolin-12- newline(6H)-on (RLX) and 10, 11-dimethoxy-4, 4, 4a, 7, 12-pentamethyl-2, 3, 4, 4a, 5, 6, 7,12c octahydro-1H nzo[3,4]cyclohepta[1,2-b]benzofuran-9-carbaldehyde (MPL) newlinerespectively, to target central element of PI3K signaling pathway. newlineIn an attempt, we screened Quinazoline and Meroterpenoid derivatives against a newlinepanel of cancer cells i.e. Leukemia (THP-1), Prostate (PC-3), Breast (MCF-7, T47D), newlinePancreas (MIAPaca-2), Colon (HCT-116, Caco-2, Colo 205) cancer cells and normal newlineepithelial cell (fR-2) as well, for anticancer activity. Herein, we found that towards newlinethe test compounds consisting of Quinazoline and Meroterpenoid as their backbone scaffolds, cell proliferation exhibited specific discrepancy in sensitivity of colon cancer cell lines (HCT-116 and Caco-2).Taken together, these findings highlighted that the RLX and MPL inhibits newlinePI3K/Akt/FoxO3a signalling as evaluated by the direct silencing and expression newlinemodel assays under in vitro and in vivo conditions. This was associated with the newlineinduction of profound apoptosis and the tumor regression in in vivo murine models. newlineSo, the present studies bear significant potential of exploring the future studies for the possible role of RLX and MPL as anti-cancer chemotherapeutic agent for the newlinetreatment of the colorectal carcinoma.
Appears in Departments:Department of Biochemistry

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1. introduction.pdfAttached File648.99 kBAdobe PDFView/Open
2. review of litrature.pdf1.45 MBAdobe PDFView/Open
3. materials and methods.pdf861.19 kBAdobe PDFView/Open
4. result.pdf3.62 MBAdobe PDFView/Open
5. discussion.pdf485.94 kBAdobe PDFView/Open
6. summary thesis.pdf516.71 kBAdobe PDFView/Open
7.references.pdf401.54 kBAdobe PDFView/Open
contents.pdf487.83 kBAdobe PDFView/Open
credentials.pdf527.53 kBAdobe PDFView/Open
table, figures and abberavations.pdf608.12 kBAdobe PDFView/Open
tittle page.pdf177.7 kBAdobe PDFView/Open

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