ANTITUMOR AND ANTIVIRAL NUCLEOSIDE ANALOGS

新的核苷类似物将被制备和研究作为潜在的 抗肿瘤剂和抗病毒剂。 这些化合物将包括： 腺苷和胞苷的“羟基碳环”类似物，（ii） 抗肿瘤和抗病毒剂araC的羟基碳环类似物 [阿糖胞苷，1-（β-D-阿拉伯呋喃糖基）胞嘧啶]和araA [阿糖胞苷， 9-（β-D-阿拉伯呋喃糖基）-腺嘌呤]，与 抗肿瘤核苷类抗生素，和（iii）奈普拉诺菌素A（NPC-A）， 相应的胞苷类似物。 所有化合物将通过化学方法获得 以反-7-叔丁氧基-5-环己烯-外-顺-2，3-二醇为键的合成 普通中间体 NPC-A及其合成类似物的抗肿瘤活性和作用机制 将在小鼠白血病L1210、P388和 十六个实体肿瘤系统。 将特别注意（i） 抑制大分子合成，（ii）逆转研究与特定的 代谢物，（iii）核苷酸库大小的改变，和（iv）影响 RNA的成熟。 核苷类似物的抗病毒活性也将 追究

Novel nucleoside analogs will be prepared and studied as potential antitumor and antiviral agents. These compounds will include: (i) "Hydroxycarbocyclic" analogs of adenosine and cytidine, (ii) Hydroxycarbocyclic analogs of antitumor and antiviral agents araC [Cytarabine, 1-(Beta-D-arabinofuranosyl)cytosine] and araA [Vidarabine, 9-(Beta-D-arabinofuranosyl)-adenine] related to the neplanocin group of antitumor nucleoside antibiotics, and (iii) neplanocin A (NPC-A) and the corresponding cytidine analog. All compounds will be obtained by chemical synthesis using anti-7-tert-butoxy-5-norbornene-exo-cis-2,3-diol as a key common intermediate. Antitumor activity and mechanism of action of NPC-A and synthetic analogs will be studied in vitro and in vivo in murine leukemia L1210, P388, and sixteen solid tumor systems. Particular attention will be paid to (i) inhibition of macromolecular synthesis, (ii) reversal studies with specific metabolites, (iii) alterations in nucleotide pool sizes, and (iv) effects on RNA maturation. Antiviral activity of the nucleoside analogs will also be investigated.