Take Y, Oogose K, Kubo T, Inouye Y, Nakamura S, Kitahara Y, Kubo A
J Antibiot (Tokyo). 1987 May;40(5):679-84. doi: 10.7164/antibiotics.40.679.
Thirteen heterocyclic quinones (5 quinoline quinones, 7 isoquinoline quinones, 1 indole quinone) were tested for their effects on avian myeloblastosis virus reverse transcriptase, growth of murine lymphoblastoma L5178Y cells, respiration of rat liver mitochondria and oxidation of NADH by Clostridium kluyveri diaphorase in comparison with those of streptonigrin, in which the quinoline quinone moiety is considered to play a crucial role. Most of the quinoline quinones and isoquinoline quinones inhibited reverse transcriptase to the same extent as streptonigrin with the ID50 values ranging between 1 and 5 micrograms/ml, whereas the ID50 value of the indole quinone derivative, 4,7-dihydro-2,3-dimethylindole-4,7-dione, was 80 micrograms/ml. The cytotoxicities of the quinones were much lower than that of streptonigrin; the ID50 values of the quinones were higher than 0.15 micrograms/ml. In particular, the ID50 value of the ortho-quinoline quinone derivative, 8-methoxy-7-methyl-5,6-dihydroquinoline-5,6-dione, was as high as 16 micrograms/ml, while the 50% inhibition of cell growth was seen in the presence of 0.0025 micrograms/ml streptonigrin. The membrane transport of the quinones was evaluated by comparing the effects on oxygen consumption by mitochondria and oxidation of NADH by bacterial diaphorase, being proven not to be responsible for their lower cytotoxicities.
测试了13种杂环醌（5种喹啉醌、7种异喹啉醌、1种吲哚醌）对禽成髓细胞瘤病毒逆转录酶的影响、对小鼠淋巴瘤L5178Y细胞生长的影响、对大鼠肝线粒体呼吸作用的影响以及对克氏梭菌黄递酶氧化NADH的影响，并与链黑菌素进行了比较，其中喹啉醌部分被认为起关键作用。大多数喹啉醌和异喹啉醌对逆转录酶的抑制程度与链黑菌素相同，半数抑制浓度（ID50）值在1至5微克/毫升之间，而吲哚醌衍生物4,7 - 二氢 - 2,3 - 二甲基吲哚 - 4,7 - 二酮的ID50值为80微克/毫升。醌类的细胞毒性远低于链黑菌素；醌类的ID50值高于0.15微克/毫升。特别是邻喹啉醌衍生物8 - 甲氧基 - 7 - 甲基 - 5,6 - 二氢喹啉 - 5,6 - 二酮的ID50值高达16微克/毫升，而在存在0.0025微克/毫升链黑菌素的情况下可观察到50%的细胞生长抑制。通过比较对线粒体耗氧量和细菌黄递酶氧化NADH的影响来评估醌类的膜转运，结果表明其较低的细胞毒性并非由此导致。
