ACTIVITY OF FLUOROQUINOLONE ANTIBIOTICS AGAINST PLASMODIUM-FALCIPARUM INVITRO
ACTIVITY OF FLUOROQUINOLONE ANTIBIOTICS AGAINST PLASMODIUM-FALCIPARUM INVITRO
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DOI：
10.1128/aac.32.8.1182
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发表时间：
1988-08-01
影响因子：
4.9
通讯作者：
BIA, FJ
中科院分区：
文献类型：
--
作者：
DIVO, AA;SARTORELLI, AC;BIA, FJ
氟喹诺酮类抗生素在结构上与萘啶酸相关。它们的主要抗菌作用似乎主要是由于抑制DNA回旋酶（DNA拓扑异构酶II）。我们测定了几种氟喹诺酮类药物对两种恶性疟原虫FCC1（氯喹敏感）和VNS（氯喹抗性）的体外活性。在48和96 h测定疟原虫的[3H]次黄嘌呤掺入。与无药物对照相比，每种药物导致[3H]次黄嘌呤掺入减少50%的摩尔浓度定义为50%抑制浓度。评价的氟喹诺酮类药物为阿米替林、环丙沙星、依诺沙星、诺氟沙星、氧氟沙星和培氟沙星。测试的其他DNA促旋酶抑制剂是萘啶酸、新生霉素和香豆霉素A1。在氟喹诺酮类药物中，环丙沙星在48小时时对氯喹敏感和抗性的恶性疟原虫菌株均具有最低的50%抑制浓度，（0.26 ± 0.05）。0.08）×10-4和（0.38 . ±. 0.15）×10-4 M，分别为（平均值±.标准偏差）。依诺沙星对FCC1和VNS在96小时具有最低的50%抑制浓度，0.23 ×10-5和（0.06 ±. 0.04）×10-5 M，分别。对于VNS菌株，环丙沙星和四环素组合的部分抑制浓度指数在48和96小时分别计算为0.93和0.79，表明适度的累加效应。新生霉素与环丙沙星的组合在同一系统中显示无差异。某些氟喹诺酮类药物的抗疟作用在可达到的血清浓度下发生。DNA促旋酶的抑制是否有助于氟喹诺酮类药物的抗疟活性目前尚不清楚。
The fluoroquinolone antibiotics are structurally related to nalidixic acid. Their primary antibacterial action appears to be mainly due to inhibition of DNA gyrase (DNA topoisomerase II). We determined the activity of several fluoroquinolones in vitro against two strains of Plasmodium falciparum, FCC1 (chloroquine susceptible) and VNS (chloroquine resistant). [3H]hypoxanthine incorporation by malarial parasites was determined at 48 and 96 h. The molarity at which each agent caused a 50% decrease in the incorporation of [3H]hypoxanthine compared with that of drug-free controls was defined as the 50% inhibitory concentration. The fluoroquinolones evaluated were amifloxacin, ciprofloxacin, enoxacin, norfloxacin, ofloxacin, and pefloxacin. Other DNA gyrase inhibitors tested were nalidixic acid, novobiocin, and coumermycin A1. Among the fluoroquinolones, ciprofloxacin had the lowest 50% inhibitory concentrations at 48 h against both chloroquine-susceptible and -resistant strains of P. falciparum, (0.26 .+-. 0.08) .times. 10-4 and (0.38 .+-. 0.15) .times. 10-4 M, respectively (mean .+-. standard deviation). Enoxacin had the lowest 50% inhibitory concentrations against FCC1 and VNS at 96 h, 0.23 .times. 10-5 and (0.06 .+-. 0.04) .times. 10-5 M, respectively. With the VNS strain, fractional inhibitory concentration indexes for the combination of ciprofloxacin and tetracycline were calculated at 48 and 96 h to be 0.93 and 0.79, respectively, indicating modest additive effects. The combination of novobiocin with ciprofloxacin showed indifference in the same system. The antimalarial effects of some fluoroquinolones occur at achievable serum concentrations. Whether inhibition of DNA gyrase contributes to the antimalarial activity of the fluoroquinolones is unknown at present.