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Design, Synthesis and Evaluation of Novel Taxane-Based Anticancer Agents

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dc.contributor.advisor Iwao Ojima. en_US
dc.contributor.author Li, Yuan en_US
dc.contributor.other Department of Chemistry en_US
dc.date.accessioned 2012-05-17T12:21:12Z
dc.date.accessioned 2015-04-24T14:48:21Z
dc.date.available 2012-05-17T12:21:12Z
dc.date.available 2015-04-24T14:48:21Z
dc.date.issued 2011-05-01
dc.identifier Li_grad.sunysb_0771E_10506.pdf en_US
dc.identifier.uri http://hdl.handle.net/1951/56053 en_US
dc.identifier.uri http://hdl.handle.net/11401/71643 en_US
dc.description.abstract Taxol¶© (paclitaxel) and TaxotÇùre¶© (docetaxel) are the most widely used pharmaceuticals in cancer chemotherapy. These drugs have been approved by the FDA for the treatment of advanced ovarian cancer, metastatic breast cancer, Kaposi Sarcoma, non-small cell lung cancer, etc. Both drugs are also under clinical development for additional cancer indications. Although established great success in the clinic, paclitaxel and docetaxel have exhibited a number of undesirable side effects as well as low efficiency against drug-resistant cancerphenotypes. Therefore the development of new analogs, which are expected to have higher potency and better pharmacological properties but fewer side effects, is of high value from the cancer chemotherapy perspective. The dissertation will present the design, synthesis and biological evaluation of the following novel taxane-based anticancer agents: (1) New generation taxoids: via the highly efficient β-Lactam Synthon Method, the design and synthesis of a large number of novel taxoids with systematic modifications has led to the development of highly potent second- and third-generation taxoids. In parallel, taxoids against multi-drug resistance cell lines have also been developed to create the dual functions (the cytotoxicity and the MDR reversal activity) into one molecule. (2) Macrocyclic taxoids: paclitaxel takes effect by inducing microtubule stabilization, G2/M block and apoptosis. Although this classic mechanism of action has been known for almost 30 years, the binding conformation of paclitaxel to β-tubulin is yet to be fully understood. Structurally constrained macrocyclic taxoids were designed, synthesized and evaluated to help identify the bioactive conformation(s). (3) Novel taxoid conjugates: the undesirable side effects in conventional cancer chemotherapy are generally resulted from the lack of tumor-specificity. Omega-3 fatty acids have been shown to be beneficial for tumor-targeting drug delivery. Novel tumor-targeting conjugates of new generation taxoids were hence designed and synthesized using omega-3 polyunsaturated fatty acids. en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Chemistry -- Organic Chemistry en_US
dc.subject.other anticancer, synthesis, taxane-based, taxoids en_US
dc.title Design, Synthesis and Evaluation of Novel Taxane-Based Anticancer Agents en_US
dc.type Dissertation en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Dale G. Drueckhammer en_US
dc.contributor.committeemember Kathlyn A. Parker en_US
dc.contributor.committeemember Michael R. Angelastro. en_US

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