ANTIMALARIAL ACTIVITY OF WR-243251, A DIHYDROACRIDINEDIONE
ANTIMALARIAL ACTIVITY OF WR-243251, A DIHYDROACRIDINEDIONE
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DOI：
10.1128/aac.38.8.1753
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发表时间：
1994-08-01
影响因子：
4.9
通讯作者：
ROSSAN, R
中科院分区：
文献类型：
--
作者：
BERMAN, J;BROWN, L;ROSSAN, R
WR 243251是一种二氢吖啶二酮，已在体外和体内评价了其抗疟疾血液原虫活性。计算杀死50%生物体的体外剂量为11 nM的氯喹敏感，甲氟喹耐药的标准菌株和25 nM的氯喹和乙胺嘧啶耐药的标准菌株。治愈100%感染伯氏疟原虫药物敏感株的小鼠所需的口服和皮下给药总剂量为12至20 mg/kg体重。治愈100%感染恶性疟原虫的Aotus猴所需的方案为8 mg/kg/天，持续3天（氯喹敏感株）和16 mg/kg/天，持续3天（氯喹抗性株）。对于先前暴露于亚治疗剂量的寄生虫，Aotus猴的100%治疗剂量未增加。WR 243251的治愈剂量的绝对值与临床抗疟药的值相当或更低。高绝对活性、对易感和耐药寄生虫活性的可比性以及暴露于亚治疗剂量不能诱导耐药性表明WR 243251具有作为血液杀寄生虫剂的强大潜力。
WR 243251 is a dihydroacridinedione that was evaluated for antimalarial blood schizonticidal activity in vitro and in vivo. The in vitro doses calculated to kill 50% of organisms were 11 nM for a chloroquine-susceptible, mefloquine-resistant standard strain and 25 nM for a chloroquine- and pyrimethamine-resistant standard strain. The total dose needed to cure 100% of mice infected with a drug-susceptible strain of Plasmodium berghei was 12 to 20 mg/kg of body weight for both oral and subcutaneous administration. The regimen needed to cure 100% of Aotus monkeys infected with Plasmodium falciparum was 8 mg/kg/day for 3 days (chloroquine-susceptible strain) and 16 mg/kg/day for 3 days (chloroquine-resistant strain). The 100% curative doses for Aotus monkeys did not increase for parasites previously exposed to subcurative doses. The absolute value of the curative doses of WR 243251 was comparable to or lower than the values for clinical antimalarial agents. The high absolute activity, comparability of activities against susceptible and resistant parasites, and inability to induce resistance by exposure to subcurative doses suggest that WR 243251 has strong potential as a blood schizonticidal agent.