Mazerski J, Cybulska B, Bolard J, Borowski E
Drugs Exp Clin Res. 1986;12(6-7):627-33.
The haemolytic activity of aromatic heptaene antifungal antibiotics (vacidin A and its analogues) can be decreased by chemical modification. It has been shown that the ionic state of the polar head of the antibiotic molecule is essential for this activity. The effect of the net charge of the antibiotic molecule on association constant, K, between polyene and membrane-located cholesterol; and the number, n, of antibiotic molecules per one erythrocyte critical for lysis induction was investigated. In addition, changes in the structure of the polyene-cholesterol complex were monitored by circular dichroism spectroscopy. Zwitterionic native antibiotics (vacidin A and gedamycin), the negatively charged N'-acetyl derivatives and the positively charged methyl esters were used in these studies. The results presented indicate that two different phenomena are responsible for the decrease in the haemolytic activity of the compounds studied: for N'-acetyl derivatives the decrease of activity is mainly a result of lower affinity of negatively charged molecules to the membranes; for methyl esters the drastic decrease of activity is mainly a result of the different structure of the antibiotic-cholesterol complex. The permeabilizing species formed from these complexes are characterized by very low efficiency of ion permeation.
芳香族七烯类抗真菌抗生素（瓦西地菌素A及其类似物）的溶血活性可通过化学修饰降低。研究表明，抗生素分子极性头部的离子状态对该活性至关重要。研究了抗生素分子净电荷对多烯与膜结合胆固醇之间的缔合常数K以及每个红细胞中诱导溶血所需抗生素分子数n的影响。此外，通过圆二色光谱监测多烯 - 胆固醇复合物结构的变化。两性离子天然抗生素（瓦西地菌素A和格达霉素）、带负电荷的N'-乙酰衍生物和带正电荷的甲酯用于这些研究。给出的结果表明，所研究化合物溶血活性降低有两种不同现象：对于N'-乙酰衍生物，活性降低主要是由于带负电荷分子与膜的亲和力较低；对于甲酯，活性急剧降低主要是由于抗生素 - 胆固醇复合物的不同结构。由这些复合物形成的通透物种的特征是离子渗透效率非常低。
