Schwartz P M, Shipman C, Drach J C
Antimicrob Agents Chemother. 1976 Jul;10(1):64-74. doi: 10.1128/AAC.10.1.64.
The antiviral activity of the fraudulent nucleoside arabinosyladenine (ara-A) against herpes simplex virus (HSV) type 1 was increased nearly 20-fold by the adenosine deaminase inhibitor, coformycin. The combination of ara-A plus coformycin was 90 times more potent in blocking HSV replication than was arabinosylhypoxanthine (ara-H). In suspension culture both drugs were more active than they were in monolayer culture. Deoxyribonucleic acid (DNA) synthesis also was inhibited by the nucleosides. Depending upon the species of DNA examined, ara-A was 8 to 15 times more active in the presence of coformycin, and the combination was 35 to 70 times more potent than ara-H. Both drugs inhibited total DNA synthesis to the same extent in uninfected and HSV-infected KB cells. In contrast, viral DNA synthesis was three to six times more susceptible to inhibition than was cellular DNA synthesis. Inhibition of viral DNA synthesis was more pronounced in suspension culture than in monolayer culture. However, the method of cell propagation did not alter the degree to which the drugs inhibited DNA synthesis in uninfected KB cells. An index has been derived to quantitate the extent of the selective inhibition of viral or cellular DNA synthesis. Fifty percent inhibitory concentrations of a drug were calculated for uninfected KB DNA synthesis and viral DNA synthesis and expressed as a ratio. The logarithm of this ratio was termed the selective index and was positive if viral DNA synthesis was inhibited preferentially or negative if uninfected KB DNA synthesis was more strongly inhibited. Data from experiments performed in monolayer culture gave positive selective index values of 0.3, 0.5, and 0.4 for ara-A plus coformycin, ara-A, and ara-H, respectively. Values of 0.7 and 0.6 were obtained from suspension culture data for ara-A plus coformycin and ara-H, respectively. Considered collectively, the data presented in this communication establish that coformycin increased the potency of ara-A but did not increase its selectivity.
腺苷脱氨酶抑制剂助间霉素可使伪核苷阿糖腺苷（ara - A）对1型单纯疱疹病毒（HSV）的抗病毒活性提高近20倍。阿糖腺苷与助间霉素联合使用在阻断HSV复制方面的效力比阿糖次黄嘌呤（ara - H）强90倍。在悬浮培养中，两种药物的活性均高于单层培养。核苷也可抑制脱氧核糖核酸（DNA）合成。根据所检测的DNA种类，在有助间霉素存在的情况下，阿糖腺苷的活性高8至15倍，且联合用药比阿糖次黄嘌呤的效力强35至70倍。两种药物在未感染和HSV感染的KB细胞中对总DNA合成的抑制程度相同。相比之下，病毒DNA合成比细胞DNA合成对抑制作用更敏感三至六倍。病毒DNA合成的抑制在悬浮培养中比在单层培养中更明显。然而，细胞增殖方法并未改变药物对未感染KB细胞中DNA合成的抑制程度。已得出一个指数来定量病毒或细胞DNA合成的选择性抑制程度。计算未感染KB DNA合成和病毒DNA合成的药物半数抑制浓度，并表示为一个比值。该比值的对数称为选择性指数，如果病毒DNA合成被优先抑制则为正值，如果未感染KB DNA合成被更强抑制则为负值。在单层培养中进行的实验数据显示，阿糖腺苷与助间霉素、阿糖腺苷和阿糖次黄嘌呤的选择性指数正值分别为0.3、0.5和0.4。从悬浮培养数据中分别获得阿糖腺苷与助间霉素和阿糖次黄嘌呤的选择性指数值为0.7和0.6。总体而言，本通讯中呈现的数据表明助间霉素提高了阿糖腺苷的效力，但未提高其选择性。
