SYNTHESIS OF MESOIONIC NUCLEOSIDES AS ANTINEOPLASTIC AND ANTIMICROBIAL AGENTS

作为抗肿瘤和抗菌剂的介离子核苷的合成

• 批准号: 6107562
• 负责人: GODWIN Okechukwu MBAGWU
• 金额: --
• 依托单位: VIRGINIA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 1999-04-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6107562
• 关键词: CHO cells; Trypanosoma; antiinfective agents; antineoplastics; antiprotozoal agents; chemical condensation; chemical synthesis; drug design /synthesis /production; glycosides; infrared spectrometry; laboratory mouse; mass spectrometry; minority institution research support; nonhuman therapy evaluation; nuclear magnetic resonance spectroscopy; nucleoside analog; ultraviolet spectrometry; xanthines

A novel series of mesoionic xanthine-based acyclonucleosides will be synthesized, characterized and investigated as potential antiprotozoan agents in vitro and in vivo and as potential antitumor agents in vitro. The nucleoside analogues, by modification of the activity of the enzymes of nucleic acid biosynthesis, provide some of the most powerful and useful inhibitors of viral replication and neoplastic tissue growth. Fertile though the nucleoside field has been, most of the existing antibiotic purine and pyrimidine nucleosides are associated with serious toxicity. In addition, resistance to them is becoming an increasing problem. Intensive efforts to find structurally-related more selective and effective therapeutic alternatives have been underway in various laboratories in the past decade and it remains an unmet need of antiviral and cancer chemotherapy in the 1990s. Although a number of mesoionic xanthine nucleoside analogues with modifications being made in the heterocyclic base and/or the sugar moiety have been previously investigated for their antiviral or cytostatic activities, mesoionic derivatives containing acyclic carbohydrate moiety as proposed in the present study, have not been described. The mesoionic compounds will be prepared by cyclocondensation of appropriate protected glycoside precursors with malonic ester, substituted malonic esters or chlorocarbonylphenyl ketene followed by deprotection with dimethylamine. The synthesized compounds will be characterized spectroscopically by proton magnetic resonance (1 H NMR), carbon-13 magnetic resonance (13C NMR), mass spectrometry (MS), ultraviolet spectroscopy (UV), infrared spectroscopy (IR) and carbon, hydrogen, nitrogen elemental analysis.

一系列新颖的基于中离子黄嘌呤的无环双糖苷将被 作为潜在的抗原动物进行了合成、表征和研究 在体外和体内的代理和作为潜在的抗肿瘤剂在体外。 核苷类似物，通过改变酶的活性 核酸生物合成，提供了一些最强大和有用的 抑制病毒复制和肿瘤组织生长。 肥沃 虽然核苷领域已经，大多数现有的抗生素， 嘌呤和嘧啶核苷具有严重的毒性。 此外，对它们的耐药性正在成为一个日益严重的问题。 加紧努力，寻找结构相关的更具选择性和 有效的治疗替代方案已经在各种 在过去的十年里，它仍然是一个未得到满足的抗病毒需求 和癌症化疗。 虽然许多具有中离子型的黄嘌呤核苷类似物， 在杂环碱基和/或糖部分中进行修饰 先前已经研究了它们的抗病毒性或细胞抑制性 活性，含有无环碳水化合物部分的介离子衍生物 在本研究中提出的，没有被描述。 介离子 化合物将通过适当的保护的环化缩合来制备。 糖苷前体与丙二酸酯、取代的丙二酸酯或 氯羰基苯基乙烯酮，然后用二甲胺脱保护。 所合成的化合物将通过以下光谱表征： 质子核磁共振（1H NMR）、碳-13核磁共振（13 C NMR）、质谱法（MS）、紫外光谱法（UV）、红外光谱法（IR）、质谱法（MS）、质谱法（MS）、质谱法（MS）、紫外光谱法（UV）、红外光谱法（IR）。 红外光谱和碳、氢、氮元素分析。