Discovery of Novel Benzo[a]phenoxazine SSJ-183 as a Drug Candidate for Malaria
Discovery of Novel Benzo[a]phenoxazine SSJ-183 as a Drug Candidate for Malaria
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DOI：
10.1021/ml100120a
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发表时间：
2010-10-01
影响因子：
4.2
通讯作者：
Ihara, Masataka
中科院分区：
文献类型：
--
作者：
Ge, Jian-Feng;Arai, Chika;Ihara, Masataka
疟疾是热带、亚热带地区由原虫寄生虫引起的严重传染病。由于旅行和全球变暖，即使是温带地区的居民也面临感染疟疾的危险。治疗疟疾和疟疾需要新颖、有效、安全和廉价的药物。 。为全球根除目标做出贡献。寻找新的抗疟药的方法是通过生物学评价进行合成。具有 4-氨基吡啶基团的衍生物 SSJ-183(5) 对恶性疟原虫的 IC50 值为 7.6 nM，选择性指数 > 7300：对感染伯氏疟原虫 ANKA 菌株的小鼠口服 3 次 100 mg/kg 5 剂量即可治愈。 5的安全性得到了单剂量高达2000 mg/kg口服的小鼠急性毒性试验、染色体畸变试验、体外和体内微核试验以及小鼠光毒性研究的支持。因此，5是一种有前途的新型抗疟药物候选者。
Malaria is a serious infectious disease caused by protozoan parasites in tropical and subtropical regions. Even inhabitants of temperate zones are exposed to the danger of malaria infection because of travel and global warming. Novel, effective,safe, and inexpensive drugs are required to treat malaria and. . contribute to the global goal of eradication. A search for new antimalarial-agents has by the synthesis of by biological evaluations. The derivative SSJ-183(5) having a 4-aminopyridine group, showed an IC50 value against Plasmodium falciparum of 7.6 nM and a selectivity index of > 7300: Cure was acheived by three oral doses of 5 at 100 mg/kg to mice infected with the Plasmodium berghei ANKA strain. The safety of 5 was supported acute toxicity testing in mice with single doses up to 2000 mg/kg po, chromosome aberration test, in vitro as well as in vivo micronucleus tests and phototoxicity studies in mice. Thus, 5 is a promising candidate as a new antimalarial agent.