ANTIMALARIAL ACTIVITY AND INHIBITION OF MONOAMINE OXIDASE-A AND OXIDASE-B BY EXO-ERYTHROCYTIC ANTIMALARIALS - OPTICAL ISOMERS OF PRIMAQUINE, N-ACYLATED CONGENERS, PRIMAQUINE METABOLITES AND 5-PHENOXY-SUBSTITUTED ANALOGS
ANTIMALARIAL ACTIVITY AND INHIBITION OF MONOAMINE OXIDASE-A AND OXIDASE-B BY EXO-ERYTHROCYTIC ANTIMALARIALS - OPTICAL ISOMERS OF PRIMAQUINE, N-ACYLATED CONGENERS, PRIMAQUINE METABOLITES AND 5-PHENOXY-SUBSTITUTED ANALOGS
复制标题
DOI：
10.1016/0014-5793(87)80072-8
复制
发表时间：
1987-04-20
期刊：
影响因子：
3.5
通讯作者：
ABELL, CW
中科院分区：
文献类型：
--
作者：
BROSSI, A;MILLET, P;ABELL, CW
当伯喹侧链上的末端氨基被2中所示的乙氧基乙酰基封闭，或通过氧化脱氨基生成羧酸3而被消除时，在检测组织裂殖体活性的筛选试验中，抗疟作用显著降低。伯喹的光学异构体1A和1B具有与外消旋混合物相似的抗疟疾活性，但1B的毒性较小。5-苯氧基取代类似物4属于一类新的抗疟药，在测定中显示出与1A或1B相似的效力，但似乎比(±)-伯氨喹的细胞毒性小。化合物1A和1B对人单胺氧化酶(MAO)A和B(Kirang103-225μM)具有竞争性抑制作用，但4种化合物对MAO A(Ki=6.8μM)和MAO B的非竞争性抑制(Ki=2.3μM)分别有10~30倍和40~90倍的非竞争性抑制作用。
When the terminal amino group in the side chain of primaquine was blocked with an ethoxyacetyl group shown in 2, or eliminated by oxidative deamination to carboxylic acid 3, the antimalarial effect was markedly reduced in a screening assay which measures tissue schizonticidal activity. The optical isomers 1A and 1B of primaquine had similar antimalarial potency to the racemic mixture but 1B appeared less toxic. The 5‐phenoxy‐substituted analogue 4, belonging to a new class of antimalarials, showed similar potency in the assays to either 1A or 1B but seemed less cytotoxic than (±)‐primaquine. Compounds 1A and 1B were found to be competitive inhibitors of human monoamine oxidase (MAO) A and B (Kirange 103–225 μM), but 4 showed 10–30‐fold greater competitive inhibition of MAO A (Ki= 6.8 μM) and 40–90‐fold greater non‐competitive inhibition of MAO B (Ki= 2.3 μM).