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synthesis and studies of a quinone methide model for the anthracycline antitumor antibiotics. [microform]
synthesis and studies of a quinone methide model for the anthracycline antitumor antibiotics. [microform]
상세정보
- 자료유형
- 마이크로피시
- 청구기호
- 저자명
- 서명/저자
- synthesis and studies of a quinone methide model for the anthracycline antitumor antibiotics. - [microform]
- 발행사항
- 형태사항
- 162 p. : microfiches ; 11×15 cm
- 총서명
- UMI Dissertation
- 주기사항
- Source: Dissertation Abstracts International, Volume: 58-02, Section: B, page: 0712.
- 학위논문주기
- thesis (ph.d.)-- - university of california, riverside, 1997.
- 초록/해제
- 요약The anthracycline antitumor antibiotics are an important class of drugs in the fight against cancer. Though in wide clinical use, the precise mode of action of these drugs is poorly understood. The objective of our research was to synthesize and study quinone methide models for the anthracyclines. Our work is presented here with a review of anthracycline history and modes of action.
- 초록/해제
- 요약Chapter 1. The introduction to the first chapter presents a brief history of the discovery adriamycin and daunomycin, a review of their biological activity, a description of how their structures may relate to biological activity, and a discussion of how these drugs intercalate DNA. The second portion of the first chapter reviews the possible modes of action of the anthracyclines including: (1) a radical-based mechanism; (2) a pathway involving DNA Topoisomerase II; or (3) a mechanism involving formation of quinone methide intermediates.
- 초록/해제
- 요약Chapter 2. Our research originated with the idea that it is important to understand the chemistry of the quinone methides even if these intermediates are not related to the anticancer properties of the anthracyclines. If indeed they are responsible for all or part of the anticancer properties, an even stronger reason exists to study their chemistry. In addition, by gaining a firm understanding of the chemistry of the quinone methides, new anthracyclines might be designed that maximize the desired anticancer properties and minimize the undesired cytotoxic side effects.
- 초록/해제
- 요약To examine the role of these intermediates in the biological activity of the anthracyclines, we have constructed model quinone methide 47 and investigated the addition of a range of nucleophiles to it. We rescaled and revised Rainier's modifications of Hauser's procedures for the synthesis of bis-pivalate 68. With a quantity of bis-pivalate 68 on hand, we were able to synthesize and characterize several heteroatom- and carbon-based nucleophile adducts with quinone methide 47. Additionally, we successfully added a nucleoside $(3\sp\prime,5\sp\prime$-bis- (t-butyldimethylsilyl) -2$\sp\prime$-deoxyadenosine) and a thiosugar $(\beta$-D-thioglucose tetraacetate) to the quinone methide. Eventually, a clear picture emerged where the addition of nucleophiles and adduct stability favored C $$ S $$ N $$ O, with the relative stability of the aniline and ethanol adducts difficult to assess.
- 복제주기
- Microfiche : UMI . microfiches;11×15 cm.
- 일반주제명
- 일반주제명
- 일반주제명
- 키워드
- 기타저자
- 기본자료저록
- Dissertation Abstracts International. 58-02B.
MARC
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■001AAV9723705
■00520010328163451
■008970923s us eng
■035 ▼a(UnM)AAV9723705
■040 ▼aUnM▼cUnM▼dMOKWON
■090 ▼a540▼bW938s
■1001 ▼awoytowicz, catherine.
■24510▼asynthesis and studies of a quinone methide model for the anthracycline antitumor antibiotics.▼h[microform]
■260 ▼aU.S.▼buniversity of california▼criverside,
■300 ▼a162 p.▼bmicrofiches▼c11×15 cm
■350 ▼a$50.6
■44000▼aUMI Dissertation
■500 ▼aSource: Dissertation Abstracts International, Volume: 58-02, Section: B, page: 0712.
■502 ▼athesis (ph.d.)--▼buniversity of california▼driverside▼d1997.
■520 ▼aThe anthracycline antitumor antibiotics are an important class of drugs in the fight against cancer. Though in wide clinical use, the precise mode of action of these drugs is poorly understood. The objective of our research was to synthesize and study quinone methide models for the anthracyclines. Our work is presented here with a review of anthracycline history and modes of action.
■520 ▼aChapter 1. The introduction to the first chapter presents a brief history of the discovery adriamycin and daunomycin, a review of their biological activity, a description of how their structures may relate to biological activity, and a discussion of how these drugs intercalate DNA. The second portion of the first chapter reviews the possible modes of action of the anthracyclines including: (1) a radical-based mechanism; (2) a pathway involving DNA Topoisomerase II; or (3) a mechanism involving formation of quinone methide intermediates.
■520 ▼aChapter 2. Our research originated with the idea that it is important to understand the chemistry of the quinone methides even if these intermediates are not related to the anticancer properties of the anthracyclines. If indeed they are responsible for all or part of the anticancer properties, an even stronger reason exists to study their chemistry. In addition, by gaining a firm understanding of the chemistry of the quinone methides, new anthracyclines might be designed that maximize the desired anticancer properties and minimize the undesired cytotoxic side effects.
■520 ▼aTo examine the role of these intermediates in the biological activity of the anthracyclines, we have constructed model quinone methide 47 and investigated the addition of a range of nucleophiles to it. We rescaled and revised Rainier's modifications of Hauser's procedures for the synthesis of bis-pivalate 68. With a quantity of bis-pivalate 68 on hand, we were able to synthesize and characterize several heteroatom- and carbon-based nucleophile adducts with quinone methide 47. Additionally, we successfully added a nucleoside $(3\sp\prime,5\sp\prime$-bis- (t-butyldimethylsilyl) -2$\sp\prime$-deoxyadenosine) and a thiosugar $(\beta$-D-thioglucose tetraacetate) to the quinone methide. Eventually, a clear picture emerged where the addition of nucleophiles and adduct stability favored C $$ S $$ N $$ O, with the relative stability of the aniline and ethanol adducts difficult to assess.
■533 ▼aMicrofiche▼cUMI▼emicrofiches;11×15 cm.
■590 ▼aSchool code: 0032.
■650 4▼aChemistry, Organic
■650 4▼aChemistry, Pharmaceutical
■650 4▼aHealth Sciences, Pharmacology
■653 ▼asynthesis▼aand▼astudies▼aof▼aa▼aquinone▼amethide▼amodel▼afor▼athe▼aanthracycline▼aantitumor▼aantibiotics.
■690 ▼a0490
■690 ▼a0491
■690 ▼a0419
■71020▼auniversity of california, riverside.
■7730 ▼tDissertation Abstracts International▼g58-02B.
■790 ▼a0032
■791 ▼aPH.D.
■792 ▼a1997
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