NOVEL NUCLEOSIDES AS ANTICANCER AND ANTIVIRAL AGENTS
作为抗癌剂和抗病毒剂的新型核苷
基本信息
- 批准号:3188511
- 负责人:
- 金额:$ 13.68万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1987
- 资助国家:美国
- 起止时间:1987-08-01 至 1991-07-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
This investigation has as its goal the design and synthesis of a
series of potential anticancer and antiviral nucleoside analogues,
the evaluation of their biological activities both in vitro and in
vivo in tumor-bearing and virus infected animals, and the
elucidation of the biochemical mechanism of action(s) of their
biological activity. The approaches to be employed include the
development of methodology for the preparation of these
nucleoside analogues, their characterization by NMR, UV, mass
spectrum, and other spectrometric techniques, and the
determination of their anticancer and antiviral activities in cell
culture and in animal models.
Recently, the synthesis and antineoplastic evaluation of several
new 3'-azido and 3'-amino nucleoside analogues have been carried
out in this laboratory. Among these compounds, 3'-amino-2',
3'dideoxycytidine (3'-NH2-CdR, NSC 365107) has shown potent
inhibitory effects against L1210, P388 and Sarcoma 180 cells in
vitro. The cytotoxicity was selectively prevented by 2'-
deoxycytidine, and not by other pyrimidine deoxyribo- or
ribonucleosides, or purine nucleosides. More importantly, the 3'-
amino analogue of 2'-deoxycytidine exhibits marked anticancer
activity against both L1210 and P388 leukemias in mice. Thus
when given in a dose of 20 mg/Kg twice a day for nine
consecutive days to animals bearing the L1210 leukemia, 3'-NH2-
CdR produced cures in 80% of the treated animals, and this
regimen yielded a T/C X 100 value of 200 in mice bearing the
P388 leukemia. 3'-NH2-CdR is resistant to deamination by
purified cytidine-deoxycytidine deaminase derived from human
KB cells; both cytidine and 2'-deoxycytidine are readily
deaminated by this enzyme system. Based on these findings, the
fabrication and chemotherapeutic testing of a novel series of
nucleoside analogues are proposed in which the sugar portion is
modified and the base moeity varied. The molecular basis for the
activity of those compounds that are biologically active will be
determined.
本研究的目标是设计和合成一种
一系列潜在的抗癌和抗病毒核苷类似物,
体外和体内生物活性评价
在荷瘤和病毒感染的动物体内,
阐明其生物化学作用机制
生物活性 拟采用的方法包括
制订编写这些报告的方法
核苷类似物,它们的NMR、UV、质谱表征
光谱和其他光谱技术,以及
细胞内抗癌和抗病毒活性的测定
文化和动物模型。
最近,几个合成和评价
新的3 ′-叠氮基和3 ′-氨基核苷类似物已被提出
在这个实验室里。 在这些化合物中,3 ′-氨基-2 ′,
3'-NH2-CdR,NSC 365107,
对L1210、P388和肉瘤180细胞的抑制作用
体外 细胞毒性被2 '-
脱氧胞苷,而不是由其他嘧啶脱氧核糖或
核糖核苷或嘌呤核苷。 更重要的是,3 '-
2 ′-脱氧胞苷的氨基类似物具有显著的抗癌活性
在小鼠中抗L1210和P388白血病的活性。 因此
当以20 mg/Kg的剂量每天两次给药,
对携带L1210白血病的动物,3 '-NH 2-
CdR在80%的治疗动物中产生了治愈效果,
方案在荷瘤小鼠中产生200的T/C X 100值,
P388白血病。 3 '-NH 2-CdR对脱氨基有抗性,
纯化的人源胞苷-脱氧胞苷脱氨酶
KB细胞;胞苷和2 '-脱氧胞苷都很容易
被这种酶系统脱氨。 根据这些发现,
制造和化学治疗试验的一个新的系列,
提出了核苷类似物,其中糖部分是
改性和基础moeity变化。 的分子基础
这些具有生物活性的化合物的活性将是
测定
项目成果
期刊论文数量(6)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Synthesis and antiviral activity of several 2,5'-anhydro analogues of 3'-azido-3'-deoxythymidine, 3'-azido-2',3'-dideoxyuridine, 3'-azido-2',3'-dideoxy-5-halouridines, and 3'-deoxythymidine against human immunodeficiency virus and Rauscher-murine leukemia
3-叠氮基-3-脱氧胸苷、3-叠氮基-2,3-二脱氧尿苷、3-叠氮基-2,3-二脱氧-的几种2,5-脱水类似物的合成和抗病毒活性
- DOI:10.1021/jm00128a034
- 发表时间:1989
- 期刊:
- 影响因子:7.3
- 作者:Lin,TS;Shen,ZY;August,EM;Brankovan,V;Yang,H;Ghazzouli,I;Prusoff,WH
- 通讯作者:Prusoff,WH
Specific inhibition of DNA biosynthesis induced by 3'-amino-2',3'-dideoxycytidine.
特异性抑制 3-氨基-2,3-二脱氧胞苷诱导的 DNA 生物合成。
- DOI:10.1021/bi00424a022
- 发表时间:1988
- 期刊:
- 影响因子:2.9
- 作者:Mancini,WR;Williams,MS;Lin,TS
- 通讯作者:Lin,TS
Synthesis and antiviral activity of various 3'-azido analogues of pyrimidine deoxyribonucleosides against human immunodeficiency virus (HIV-1, HTLV-III/LAV).
嘧啶脱氧核糖核苷的各种 3-叠氮类似物的合成和抗人类免疫缺陷病毒(HIV-1、HTLV-III/LAV)的抗病毒活性。
- DOI:10.1021/jm00397a011
- 发表时间:1988
- 期刊:
- 影响因子:7.3
- 作者:Lin,TS;Guo,JY;Schinazi,RF;Chu,CK;Xiang,JN;Prusoff,WH
- 通讯作者:Prusoff,WH
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
TAI-SHUN LIN其他文献
TAI-SHUN LIN的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('TAI-SHUN LIN', 18)}}的其他基金
3'-DEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS
3-脱氧核苷类似物作为潜在的抗病毒剂
- 批准号:
3144251 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别:
3'-DEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS
3-脱氧核苷类似物作为潜在的抗病毒剂
- 批准号:
3144252 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别:
DEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS
脱氧核苷类似物作为潜在的抗病毒剂
- 批准号:
3144250 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别:
3'-DEOXYNUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS
3-脱氧核苷类似物作为潜在的抗病毒剂
- 批准号:
3144249 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别:
DEOXY NUCLEOSIDE ANALOGS AS POTENTIAL ANTIVIRAL AGENTS
脱氧核苷类似物作为潜在的抗病毒剂
- 批准号:
2064982 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别:
NOVEL NUCLEOSIDES AS ANTICANCER AND ANTIVIRAL AGENTS
作为抗癌剂和抗病毒剂的新型核苷
- 批准号:
3188510 - 财政年份:1987
- 资助金额:
$ 13.68万 - 项目类别:
NOVEL NUCLEOSIDES AS ANTICANCER AND ANTIVIRAL AGENTS
作为抗癌剂和抗病毒剂的新型核苷
- 批准号:
3188507 - 财政年份:1987
- 资助金额:
$ 13.68万 - 项目类别:
相似海外基金
The analysis of proteinuria caused by antineoplastics and the preventative effects with antihypertensive medications using the Japanese medical database
利用日本医学数据库分析抗肿瘤药物引起的蛋白尿及抗高血压药物的预防效果
- 批准号:
21K17258 - 财政年份:2021
- 资助金额:
$ 13.68万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Expediting Drug Development by Profiling Novel Antineoplastics by Mass Spectrometry-based Biomarker Profiling
通过基于质谱的生物标志物分析来分析新型抗肿瘤药物,加速药物开发
- 批准号:
499958-2016 - 财政年份:2016
- 资助金额:
$ 13.68万 - 项目类别:
Engage Grants Program
Combinatorial Peptidomimetics as Antineoplastics
作为抗肿瘤药的组合肽模拟物
- 批准号:
6623455 - 财政年份:2002
- 资助金额:
$ 13.68万 - 项目类别:
Combinatorial Peptidomimetics as Antineoplastics
作为抗肿瘤药的组合肽模拟物
- 批准号:
6465958 - 财政年份:2002
- 资助金额:
$ 13.68万 - 项目类别:
Novel Nanoparticle Delivery System for Antineoplastics
新型抗肿瘤纳米颗粒输送系统
- 批准号:
6483914 - 财政年份:2002
- 资助金额:
$ 13.68万 - 项目类别:
GLYCOLIPIDS AND CYTOTOXIC RESPONSE TO ANTINEOPLASTICS
糖脂和抗肿瘤药物的细胞毒性反应
- 批准号:
6124630 - 财政年份:1998
- 资助金额:
$ 13.68万 - 项目类别:
GLYCOLIPIDS AND CYTOTOXIC RESPONSE TO ANTINEOPLASTICS
糖脂和抗肿瘤药物的细胞毒性反应
- 批准号:
6329037 - 财政年份:1998
- 资助金额:
$ 13.68万 - 项目类别:
GLYCOLIPIDS AND CYTOTOXIC RESPONSE TO ANTINEOPLASTICS
糖脂和抗肿瘤药物的细胞毒性反应
- 批准号:
2747737 - 财政年份:1998
- 资助金额:
$ 13.68万 - 项目类别:
POLYMORPHIC METABOLISM OF ANTINEOPLASTICS IN CHILDREN
儿童抗肿瘤药物的多态性代谢
- 批准号:
3459680 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别:
POLYMORPHIC METABOLISM OF ANTINEOPLASTICS IN CHILDREN
儿童抗肿瘤药物的多态性代谢
- 批准号:
3459678 - 财政年份:1990
- 资助金额:
$ 13.68万 - 项目类别: