NEW DRUGS FOR MYCOBACTERIAL INFECTIONS IN AIDS PATIENTS

治疗艾滋病患者分枝杆菌感染的新药

• 批准号: 2672603
• 负责人: JOSEPH A MADDRY
• 金额: $ 36.3万
• 依托单位: SOUTHERN RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2672603
• 关键词: AIDS; Mycobacterium avium; Mycobacterium tuberculosis; antibacterial agents; carbohydrate metabolism; drug design /synthesis /production; drug screening /evaluation; enzyme inhibitors; microorganism culture; microorganism metabolism; oligosaccharides; opportunistic infections

DESCRIPTION: (Adapted from Applicant's Abstract). The overall objective of this application is to develop new drugs for treatment of mycobacterial infections in AIDS patients, especially M. avium (MAC) and M. tuberculosis (MTB). The target is the mycobacterial cell wall which is quite similar in both pathogens, but which contains a unique chemical structure with no counterpart in mammalian cells. This is a comprehensive program to optimize activity of compounds already developed and pursue emerging leads from more recent synthetic studies. Compounds of the following classes are to be designed and synthesized as potential antimycobacterial agents (1) Oligosaccharides congeneric to the natural substrates of the biosynthetic enzymes that can act as substrate- and bisubstrate-based inhibitors of the biosynthesis of arabinogalactan; (2) Transferase inhibitors based on the natural arabinose donor, beta-D-arabinofuranose-1-monophosphodecaprenol (DPA), a lipid conjugated arabinose donor; and (3) Transition state and bisubstrate analogs that will act as inhibitors of polysaccharide elaboration, particularly mycolylation. Synthetic compounds are to be screened against a panel of MAC and MTB strains.

描述：（改编自申请人摘要）。 的总体目标 本申请旨在开发治疗分枝杆菌感染的新药， 艾滋病患者的感染，尤其是M. avium（MAC）和M.结核 （MTB）。 目标是分枝杆菌的细胞壁， 这两种病原体，但它含有一种独特的化学结构， 哺乳动物细胞中的对应物。 这是一个全面的方案， 活性的化合物已经开发和追求新兴的线索，从更多 最近的合成研究 将使用以下类别的化合物 设计和合成为潜在的抗结核菌药物（1） 与生物合成的天然底物同源的寡聚体 酶，可以作为底物和双底物为基础的抑制剂， （2）基于阿拉伯半乳聚糖生物合成的转移酶抑制剂 天然阿拉伯糖供体，β-D-阿拉伯呋喃糖-1-单磷酸癸烯醇 (DPA)脂质缀合的阿拉伯糖供体;和（3）过渡态和 作为多糖抑制剂的双底物类似物 特别是真菌化。 合成化合物将被 针对一组MAC和MTB菌株进行筛选。

项目成果

Antimycobacterial activity of 1-deaza-7,8-dihydropteridine derivatives against Mycobacterium tuberculosis and Mycobacterium avium complex in vitro.

• DOI: 10.1093/jac/47.4.451
• 发表时间: 2001-04
• 期刊: The Journal of antimicrobial chemotherapy
• 作者: W. J. Suling;J. Maddry

Studies on alpha(1-->5) linked octyl arabinofuranosyl disaccharides for mycobacterial arabinosyl transferase activity.

• DOI: 10.1016/s0968-0896(01)00180-8
• 发表时间: 2001-12
• 期刊: Bioorganic & medicinal chemistry
• 影响因子: 3.5
• 作者: A. Pathak;V. Pathak;J. Maddry;W. J. Suling;S. Gurcha;G. Besra;R. Reynolds