Balzarini J
Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
Pharm World Sci. 1994 Apr 15;16(2):113-26. doi: 10.1007/BF01880662.
Unlike herpes viruses, human immunodeficiency virus and other retroviruses do not encode specific enzymes required for the metabolism of the purine or pyrimidine nucleotides to their corresponding 5'-triphosphates. Therefore, 2',3'-dideoxynucleosides and acyclic nucleoside phosphonates must be phosphorylated and metabolized by host cell kinases and other enzymes of purine and/or pyrimidine metabolism. Different animal species (or even different cell types within one animal species) may differ in the efficiency of conversion of these drugs to their antivirally active metabolite(s). Three 2',3'-dideoxynucleosides are officially licensed for clinical use [i.e., zidovudine (3'-azido-2',3'-dideoxythymidine, AZT), didanosine (2',3'-dideoxyinosine, DDI) and zalcitabine (2',3'-dideoxycytidine, DDC)]. A number of other 2',3'-dideoxynucleoside analogues [among them stavudine (2',3'-didehydro-2',3'-dideoxythymidine, D4T), 2',3'-dideoxy-3'-thiacytidine (3TC), 2',3'-dideoxy-5-fluoro-3'-thiacytidine (FTC) and the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA)] are currently under clinical investigation and are candidate compounds for eventual licensing as anti-AIDS drugs. The metabolic pathways, antimetabolic effects and mechanism of antiviral action of these nucleoside analogues will be discussed.
与疱疹病毒不同，人类免疫缺陷病毒和其他逆转录病毒不编码将嘌呤或嘧啶核苷酸代谢为其相应5'-三磷酸所需的特定酶。因此，2'，3'-双脱氧核苷和无环核苷膦酸盐必须由宿主细胞激酶和嘌呤和/或嘧啶代谢的其他酶进行磷酸化和代谢。不同的动物物种（甚至同一动物物种内的不同细胞类型）在将这些药物转化为其抗病毒活性代谢物的效率上可能存在差异。三种2'，3'-双脱氧核苷已正式获准用于临床[即齐多夫定（3'-叠氮基-2'，3'-双脱氧胸苷，AZT）、去羟肌苷（2'，3'-双脱氧肌苷，DDI）和扎西他滨（2'，3'-双脱氧胞苷，DDC）]。许多其他2'，3'-双脱氧核苷类似物[其中包括司他夫定（2'，3'-二脱氢-2'，3'-双脱氧胸苷，D4T）、2'，3'-双脱氧-3'-硫代胞苷（3TC）、2'，3'-双脱氧-5-氟-3'-硫代胞苷（FTC）和无环核苷膦酸盐9-（2-膦酰甲氧基乙基）腺嘌呤（PMEA）]目前正在进行临床研究，是最终获准作为抗艾滋病药物的候选化合物。将讨论这些核苷类似物的代谢途径、抗代谢作用和抗病毒作用机制。
