Cybulska B, Borowski E, Gary-Bobo C M
Department of Pharmaceutical Technology and Biochemistry, Technical University of Gdansk, Poland.
Biochem Pharmacol. 1989 Jun 1;38(11):1755-62. doi: 10.1016/0006-2952(89)90409-7.
The ionophoric and hemolytic activities of two antifungal aromatic heptaenes: vacidin A and perimycin A, were studied on human red blood cells. Measurements of hemolysis, K+ influx and efflux, H+ movement and potential difference across the cell membrane, show that the hemolytic activity, being related to the K+ permeability induced by the polyene, is strongly dependent on the ability of this polyene to induce H+ movement. It was shown that: (1) both antibiotics have approximately the same efficiency in inducing K+ permeability, but a 100-fold difference in their hemolytic activity; (2) their hemolytic activity is related to their ability to induce H+ movement; (3) the protonophoric activity requires the existence of a free carboxyl group in the macrolide ring, as in vacidin A. The hemolytic activity is determined by the intrinsic efficiency of a K+/H+ exchange induced by this polyene. With perimycin A, which lacks the free carboxyl group, the hemolytic activity is dependent on the Cl- conductive flux which slows down the K+ flux.
研究了两种抗真菌芳香族七烯类化合物——瓦西丁A和围霉素A对人红细胞的离子载体活性和溶血活性。对溶血、钾离子流入和流出、氢离子移动以及细胞膜两侧的电位差进行测量，结果表明，溶血活性与多烯诱导的钾离子通透性有关，强烈依赖于该多烯诱导氢离子移动的能力。结果显示：（1）两种抗生素诱导钾离子通透性的效率大致相同，但溶血活性相差100倍；（2）它们的溶血活性与其诱导氢离子移动的能力有关；（3）质子载体活性需要大环内酯环中存在游离羧基，如瓦西丁A。溶血活性由该多烯诱导的钾离子/氢离子交换的内在效率决定。对于缺乏游离羧基的围霉素A，溶血活性取决于减缓钾离子通量的氯离子传导通量。
