VandeWaa E A, Bennett J L, Williams J F, Satti M Z, Geary T G
Department of Microbiology and Public Health, Michigan State University, East Lansing 48824.
J Parasitol. 1989 Jun;75(3):367-72.
The potencies and efficacies of 9 quinoline-containing anti-malarials including chloroquine, (bis)desethylchloroquine, SN6911, SN12108, amodiaquine, CN-2999-2K, primaquine, quinacrine, and quinine were examined in vitro against adult female Brugia pahangi. Parasite motility and lactate excretion were measured as indicators of drug effects. All of the agents tested showed time-dependent increases in potency over a 24-72-hr incubation period. SN12108 was the most potent at 72 hr, reducing motility by greater than or equal to 50% (IC50) at 1.0 x 10(-7) M. Chloroquine (IC50 2.3 x 10(-6) M), desethylchloroquine (IC50 7.0 x 10(-6) M), quinacrine (IC50 1.9 x 10(-6) M), and quinine (IC50 1.5 x 10(-5) M) were the least potent. All of the drugs caused time-dependent decreases in lactate excretion, except quinine; decreases were found to be dose dependent. A high correlation (r greater than 0.85) was seen between time-dependent effects on motility and lactate excretion. The effects of chloroquine (10 microM) on motility were also examined in female Acanthocheilonema viteae, Dirofilaria immitis, Onchocerca volvulus, and male Onchocerca gutturosa. Dirofilaria immitis was less sensitive to chloroquine than B. pahangi; A. viteae was equally sensitive. Species of Onchocerca were the most sensitive parasites studied. Adult O. gutturosa and O. volvulus were affected by 10 microM chloroquine within 4-6 hr; motility was reduced by 80% within 24 hr. Although the mechanism of anti-filarial activity of the quinoline-containing drugs is not known, their in vitro activity against a variety of adult filariae at clinically relevant concentrations, as well as differential sensitivity seen between the different filariae examined, warrants further study of these compounds.
检测了9种含喹啉的抗疟药，包括氯喹、（双）去乙基氯喹、SN6911、SN12108、阿莫地喹、CN - 2999 - 2K、伯氨喹、喹吖因和奎宁在体外对成年雌性彭亨布鲁线虫的效力和效果。以寄生虫活力和乳酸排泄量作为药物作用的指标。在24至72小时的孵育期内，所有测试药物的效力均呈现出时间依赖性增加。SN12108在72小时时效力最强，在1.0×10⁻⁷M时使活力降低大于或等于50%（IC50）。氯喹（IC50 2.3×10⁻⁶M）、去乙基氯喹（IC50 7.0×10⁻⁶M）、喹吖因（IC50 1.9×10⁻⁶M）和奎宁（IC50 1.5×10⁻⁵M）效力最低。除奎宁外，所有药物均导致乳酸排泄量呈现时间依赖性减少；发现减少具有剂量依赖性。在对活力和乳酸排泄的时间依赖性影响之间观察到高度相关性（r大于0.85）。还检测了氯喹（10微摩尔）对雌性旋盘尾丝虫、犬恶丝虫、盘尾丝虫以及雄性喉瘤盘尾丝虫活力的影响。犬恶丝虫对氯喹的敏感性低于彭亨布鲁线虫；旋盘尾丝虫的敏感性相同。盘尾丝虫属是所研究的最敏感的寄生虫。成年喉瘤盘尾丝虫和盘尾丝虫在4至6小时内受到10微摩尔氯喹的影响；24小时内活力降低80%。尽管含喹啉药物的抗丝虫活性机制尚不清楚，但它们在临床相关浓度下对多种成年丝虫的体外活性以及在所检测的不同丝虫之间观察到的差异敏感性，值得对这些化合物进行进一步研究。
