Deng R X, Zhong J X, Zhao D C, Zhang H B, Sheng X Y, Ding D B, Yang J D
Institute of Microbiology and Epidemiology, Military Academy of Medical Sciences, Beijing 100071.
Yao Xue Xue Bao. 1997 Nov;32(11):874-8.
For the purpose of improving the oral antimalarial activities of the fluorenemethanols (reported by us in previous articles) which were less effective by oral than by subcutaneous administration, 24 alpha-(alkylaminomethyl)-2, 7-dichloro-9-substituted benzylidene-4-fluorenemethanols (III) were synthesized. The results of preliminary screenings demonstrated that five compounds (No. 1-4, 8) exhibited significant antimalarial activities against Plasmodium berghei NK65 strain in mice by oral administration, at dose of 6.25 mg.kg-1.d-1 x 3 with suppressive rate of 100%. Further evaluation of these 5 compounds showed that 4 of them (No. 1-4) were superior to chloroquine in parallel tests, their ED50 and ED90 were 1.0, 1.6; 0.6, 0.9; 0.7, 1.5 and 0.8, 1.6 mg.kg-1.d-1 x 3 respectively, while the ED50 and ED90 of chloroquine were 1.9 and 2.9 mg.kg-1. d-1 x 3 respectively; one compound (No 8) was equal to chloroquine, its ED50 and ED90 were 1.5 and 3.2 mg.kg-1.d-1 x 3 respectively. Further assessment of these 4 compounds are in progress.
为提高芴甲醇类化合物（我们之前的文章中有报道）的口服抗疟活性（该类化合物口服效果不如皮下给药），合成了24α-（烷基氨甲基）-2,7-二氯-9-取代亚苄基-4-芴甲醇（III）。初步筛选结果表明，5种化合物（编号1 - 4、8）在剂量为6.25 mg·kg⁻¹·d⁻¹×3时，对小鼠伯氏疟原虫NK65株口服给药显示出显著的抗疟活性，抑制率达100%。对这5种化合物的进一步评估表明，其中4种（编号1 - 4）在平行试验中优于氯喹，它们的ED50和ED90分别为1.0、1.6；0.6、0.9；0.7、1.5和0.8、1.6 mg·kg⁻¹·d⁻¹×3，而氯喹的ED50和ED90分别为1.9和2.9 mg·kg⁻¹·d⁻¹×3；一种化合物（编号8）与氯喹相当，其ED50和ED90分别为1.5和3.2 mg·kg⁻¹·d⁻¹×3。对这4种化合物的进一步评估正在进行中。
