Elgemeie Galal H
Chemistry Department, Faculty of Science, Helwan University, Ain-Helwan, Cairo, Egypt.
Curr Pharm Des. 2003;9(31):2627-42. doi: 10.2174/1381612033453677.
6-Mercaptopurine (6MP) and 6-thioguanine (6TG) are analogs of the natural purines: hypoxanthine and guanine. Both mercaptopurine and thioguanine are substrates for hypoxanthine-guanine phosphoribosyltransferase and are converted into the ribonucleotides 6-thioguanosine monophosphate (6-thioGMP) and 6-thioinosine monophosphate (T-IMP) respectively. The accumulation of these monophosphates inhibits several vital metabolic reactions. Today, these thiopurine bases remain valuable agents for the induction and maintenance of remissions in patients with myelocytic and acute lymphocytic leukemia. Despite their proved clinical importance, 6MP and 6TG have certain therapeutic disadvantages, which have continued to stimulate the search for purine derivatives enhancing therapeutic efficacy. Considerable efforts have been made to prepare other novel mercaptopurine and thioguanine analogs and their nucleosides to improve the antitumor efficacy. The effectiveness of these thiopurines against certain tumor cell lines suggested that some of these mercaptopurine analogs and their nucleosides would be worthy of consideration in order to determine whether they exert a more selective effect against neoplastic cells than against normal cells or they might be useful in patients whose disease has become resistant to 6MP or 6TG. This review will focus on mercaptopurine analogs and their nucleosides as antimetabolite agents.
6-巯基嘌呤（6MP）和6-硫鸟嘌呤（6TG）是天然嘌呤次黄嘌呤和鸟嘌呤的类似物。巯基嘌呤和硫鸟嘌呤都是次黄嘌呤-鸟嘌呤磷酸核糖转移酶的底物，分别转化为核糖核苷酸6-硫鸟苷单磷酸（6-硫代鸟苷酸）和6-硫代肌苷单磷酸（硫代肌苷酸）。这些单磷酸的积累会抑制几种重要的代谢反应。如今，这些硫嘌呤碱基仍然是诱导和维持粒细胞性白血病及急性淋巴细胞白血病患者缓解的重要药物。尽管6MP和6TG已被证明具有临床重要性，但它们仍存在某些治疗缺陷，这继续促使人们寻找能提高治疗效果的嘌呤衍生物。人们已付出巨大努力来制备其他新型巯基嘌呤和硫鸟嘌呤类似物及其核苷，以提高抗肿瘤疗效。这些硫嘌呤对某些肿瘤细胞系的有效性表明，为了确定它们对肿瘤细胞的作用是否比对正常细胞更具选择性，或者它们是否对已对6MP或6TG产生耐药性的患者有用，其中一些巯基嘌呤类似物及其核苷值得考虑。本综述将聚焦于作为抗代谢物的巯基嘌呤类似物及其核苷。
