ANTIMICROSPORIDIAL DRUG DISCOVERY

抗微孢子虫药物的发现

• 批准号: 7348984
• 负责人: Elizabeth Schmidt Didier
• 金额: $ 6.54万
• 依托单位: TULANE UNIVERSITY OF LOUISIANA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-05-01 至 2007-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348984
• 关键词: ANTIMICROSPORIDIAL; DRUG; DISCOVERY

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Introduction: Microsporidia are single-celled parasites that are recognized as causes of opportunistic and emerging infections in persons with AIDS, organ transplant recipients, travelers, and malnourished children. Persons with microsporidiosis usually develop persistent diarrhea, and effective therapies are lacking. Methods: Over 400 compounds were assayed in vitro against two microsporidian species which infect humans, Encephalitozoon intestinalis and Vittaforma corneae. These drugs included protease inhibitors, chitin assembly inhibitors, benzimidazoles which interfere with microtubule assembly, fumagillin-related compounds, fluoroquinolones, and triazines. Compounds that inhibited microsporidia replication by 70% at doses not toxic to the host cells were then tested for their ability to prolong survival in V. corneae-infected athymic mice. Athymic mice (groups of 8 each) were inoculated ip with 1 X 107 V. corneae spores, and drugs were administered beginning one day later. Controls received either parasites only or drug only (toxicity control). Statistically significant increases in survival times were determined by analysis of variance. Results and Discussion: Drugs that significantly (P 0.05) prolonged survival of the V. corneae-infected athymic mice included fumagillin (at 5, 10, or 20 mg/kg sq daily), the fumagillin analogue, TNP-470 (at 20 mg/kg ip daily), doxycycline (at 40 mg/kg ip daily), kanamycin (at 50, 100, or 200 mg/kg ip daily), lomefloxacin (at 100 mg/kg ip daily), norfloxacin (50 and 100 mg/kg ip daily), and gatifloxacin (25 and 50 mg/kg ip daily).

该子项目是利用 NIH/NCRR 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。简介：微孢子虫是单细胞寄生虫，被认为是艾滋病患者、器官移植接受者、旅行者和营养不良儿童中机会性和新发感染的原因。患有微孢子虫病的人通常会出现持续性腹泻，并且缺乏有效的治疗方法。 方法：在体外对 400 多种化合物进行了针对感染人类的​​两种微孢子虫（肠脑炎原虫和角膜玻璃体）的检测。这些药物包括蛋白酶抑制剂、几丁质组装抑制剂、干扰微管组装的苯并咪唑、夫马洁林相关化合物、氟喹诺酮类药物和三嗪类药物。然后测试了在对宿主细胞无毒的剂量下抑制微孢子虫复制70%的化合物延长角膜弧菌感染的无胸腺小鼠存活的能力。无胸腺小鼠（每组8只）腹膜内接种1×107角膜弧菌孢子，一天后开始给药。对照仅接受寄生虫或仅接受药物（毒性控制）。通过方差分析确定存活时间的统计学显着增加。 结果和讨论：显着（P < 0.05）延长角膜弧菌感染的无胸腺小鼠存活时间的药物包括夫马洁林（每天 5、10 或 20 mg/kg sq）、夫马洁林类似物 TNP-470（20 mg） /kg ip 每日）、强力霉素（40 mg/kg ip 每日）、卡那霉素（50 mg/kg）每日 100 或 200 mg/kg 腹腔注射）、洛美沙星（每日 ip 100 mg/kg）、诺氟沙星（每日 ip 50 和 100 mg/kg）和加替沙星（每日 ip 25 和 50 mg/kg）。