SAMPANGINES--NOVEL ANTIBIOTICS FOR AIDS-RELATED OI

Sampangines——治疗艾滋病相关成骨不全症的新型抗生素

• 批准号: 3147589
• 负责人: ALICE M. CLARK
• 金额: $ 20.63万
• 依托单位: UNIVERSITY OF MISSISSIPPI
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-07-01 至 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3147589
• 关键词: AIDS; Candida; Cryptococcus; Mycobacterium intracellulare; alkaloids; antifungal antibiotics; chemical structure function; drug design /synthesis /production; laboratory mouse; opportunistic infections; tissue /cell culture

The overall goal of this project is to prepare, from the novel class of antifungal alkaloids known as sampangines (SAMs), one or more potentially useful drugs for the treatment of certain AIDS-related opportunistic infections (OI). Currently, treatment of OI is often inadequate for a variety of reasons, including the lack of effective antimicrobial therapy. As part of a program to discover prototype antifungal antibiotics from higher plants, a novel alkaloid, 3-methoxysampangine (3-MeO-SAM), was isolated from the West African shrub, Cleistopholis patens. Preliminary studies accomplished to date have provided significant impetus for further, more extensive investigation and development of this novel class of antifungal antibiotics. Thus, we propose herein a series of chemical and biological studies that will provide the information necessary to accomplish the overall goal of developing the most effective drug(s) in this class. This major objective will be accomplished through the following specific aims: (1) Synthesize a series of rationally designed SAM structural analogs for SAR studies. (2) Evaluate the analogs from (1) for in vitro antifungal (Cryptococcus, Candida), antimycobacterial (Mycobacterium intracellulare) and antiviral (Herpes simplex virus type-1) activity. (3) Establish whether the SAMs act by a novel mechanism. (4) Assess the selectivity of the activity of the SAMs. It is anticipated that successful achievement of these specific aims will provide information necessary for the design of a clinically useful drug in this series. Further, if the SAMs are found to act by a novel antifungal mechanism, this could provide the information necessary to design a search for other such agents from natural sources.

这个项目的总体目标是准备，从小说类 抗真菌生物碱（SAM），一种或多种 治疗某些艾滋病相关疾病的潜在有用药物 机会性感染（OI）。 目前，成骨不全症的治疗方法通常是 由于各种原因，其中包括缺乏有效的 抗菌治疗。 作为发现原型计划的一部分 来自高等植物的抗真菌抗生素，一种新型生物碱， 3-甲氧基sampangine (3-MeO-SAM)，从西非分离出来 灌木，Cleistopholis patens。 初步研究已完成 日期为进一步、更广泛的 此类新型抗真菌药物的研究和开发 抗生素。 因此，我们在此提出了一系列化学和 生物学研究将提供必要的信息 实现开发最有效药物的总体目标 在这堂课上。 这一主要目标将通过 具体目标如下： (1)综合一系列合理设计的SAM结构 SAR 研究的类似物。 (2) 评估(1)中的类似物的体外抗真菌作用 （隐球菌、念珠菌）、抗分枝杆菌（分枝杆菌 细胞内）和抗病毒（1 型单纯疱疹病毒） 活动。 (3) 确定 SAM 是否通过新机制起作用。 (4) 评估 SAM 活性的选择性。 预计这些具体目标的成功实现 将为临床设计提供必要的信息 该系列中有用的药物。 此外，如果发现 SAM 的行为 通过一种新颖的抗真菌机制，这可以提供信息 有必要设计从自然中寻找其他此类药物 来源。