{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Synthesis and Biological Evaluation of Second and Third Generation of Taxoid Anticancer Agents","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/77830"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"Cancer is a group of diseases leading by uncontrolled cell growth, and is responsible for approximately one in four deaths in the United States. While significant advancements have been made in chemotherapy, combating drug resistant strains have remained a major challenge. Traditional chemotherapeutic agents, Taxol\u00ae and Taxotere\u00ae, have showed little efficacy in treating melanoma, pancreatic, gastric, brain and renal cancers. Also, in clinical treatment, repeated administration of Taxol\u00ae may lead to multi-drug resistance (MDR) phenomenon. Therefore, it is essential to develop new taxoid anticancer agents with superior pharmacological properties, fewer side effects, and improved potency against various classes of tumors, and in particular drug-sensitive and drug-resistant cancers.  On the basis of our structure-activity relationship (SAR) studies on the taxane class, three highly potent compounds - second generation taxoids SB-T-1214 and SB-T-1212N1 and third generation fluorotaxoid SB-T-121405 - were synthesized via Ojima-Holton coupling reaction using corresponding β -lactams and 10-DAB derivatives. The enantiopure β -lactams were prepared through a chiral ester enolate-imine cyclocondensation utilizing Whitesell's chiral auxiliary. The biological evaluation of taxoids by in vitro cytotoxicity assays was performed by MTT assay in cancer and drug-resistant cancer cell lines. Paclitaxel, docetaxel, SB-T-1214, and SB-T-1216 were used as control standards to evaluate the potency of eight newly synthesized taxoids, i.e., SB-T-0035, 10-Ac-docetaxel, SB-T-1211, SB-T-1212N1, SB-T-121405, SB-T-12822-6, SB-T-121406, and SB-T-12852-6. Among these compounds, SB-T-121405, with a m-OCF3 substitution at the C2 position of the taxoid, showed the highest activity against human breast carcinoma cancer cell line, MCF-7, and metastatic ovarian tumor cell line, NCI-ADR-RES."},{"label":"dcterms.available","value":"2017-09-26T17:13:38Z"},{"label":"dcterms.contributor","value":"Rudick, Jonathan"},{"label":"dcterms.creator","value":"Wang, Xin"},{"label":"dcterms.dateAccepted","value":"2017-09-26T17:13:38Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-26T17:13:38Z"},{"label":"dcterms.description","value":"Department of Chemistry."},{"label":"dcterms.extent","value":"134 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"Wang_grad.sunysb_0771M_11816.pdf"},{"label":"dcterms.issued","value":"2014-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-26T17:13:38Z (GMT). No. of bitstreams: 1\nWang_grad.sunysb_0771M_11816.pdf: 8128475 bytes, checksum: c2d796e655f58f0e676b27ff05b6bc9f (MD5)\n  Previous issue date: 2014-05-01"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Biological Evaluation, MTT assay, Synthesis, Taxoids"},{"label":"dcterms.title","value":"Synthesis and Biological Evaluation of Second and Third Generation of Taxoid Anticancer Agents"},{"label":"dcterms.type","value":"Thesis"},{"label":"dc.type","value":"Thesis"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/11%2F17%2F66%2F111766411658480650580840117255813789588/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/11%2F17%2F66%2F111766411658480650580840117255813789588","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}