Fournet A, Inchausti A, Yaluff G, Rojas De Arias A, Guinaudeau H, Bruneton J, Breidenbach M A, Karplus P A, Faerman C H
ORSTOM (Institut Français de Recherche Scientifique pour le Développement en Coopération), Asuncion, Paraguay.
J Enzyme Inhib. 1998 Feb;13(1):1-9. doi: 10.3109/14756369809035823.
Eleven bisbenzylisoquinoline (BBIQ) alkaloids were studied for in vitro trypanocidal activity against trypomastigote forms of the Y strain of Trypanosoma cruzi. The inhibitory activity of these compounds against trypanothione reductase (TR), a target enzyme for chemotherapy against Chagas disease, was also studied. Six BBIQ alkaloids (antioquine, cepharanthine, daphnoline, limacine, cycleanine and (-) curine) displayed a 50% lethal concentration (LC50) against T. cruzi of less than 100 microM. Daphnoline and curine, with LC50 values of 10 microM, are attractive for further investigation as potential anti-Chagasic drugs. Kinetic analyses suggested the BBIQ alkaloids are mixed inhibitors of TR. These compounds are reasonably potent inhibitors of TR; the best TR inhibitor, cepharanthine, had an IC50 of 15 microM, which is in the same order of magnitude as its LC50 against T. cruzi. The similar magnitudes of the IC50 and LC50 values suggest that inhibition of TR could contribute to the trypanocidal activity exhibited by the BBIQ alkaloids.
对11种双苄基异喹啉（BBIQ）生物碱进行了研究，考察其对克氏锥虫Y株锥鞭毛体形式的体外杀锥虫活性。还研究了这些化合物对锥虫硫醇还原酶（TR）的抑制活性，TR是恰加斯病化疗的靶标酶。六种BBIQ生物碱（抗疟喹、千金藤素、瑞香灵、豆甾四烯醇、环兰卡宁和（-）箭毒灵）对克氏锥虫的50%致死浓度（LC50）低于100微摩尔。瑞香灵和箭毒灵的LC50值为10微摩尔，作为潜在的抗恰加斯病药物具有进一步研究的吸引力。动力学分析表明，BBIQ生物碱是TR的混合型抑制剂。这些化合物是相当有效的TR抑制剂；最佳的TR抑制剂千金藤素的IC50为15微摩尔，与其对克氏锥虫的LC50处于同一数量级。IC50和LC50值的相似幅度表明，TR的抑制可能有助于BBIQ生物碱表现出的杀锥虫活性。
