Bioorganic Laboratory, Department of Chemistry, University of Delhi, Delhi, 110 007, India.
Department of Chemistry and Environmental Science, Medgar Evers College, 1638 Bedford Avenue, Brooklyn, NY, 11225, USA.
Top Curr Chem (Cham). 2024 Oct 23;382(4):34. doi: 10.1007/s41061-024-00476-7.
DNA is commonly known as the "molecule of life" because it holds the genetic instructions for all living organisms on Earth. The utilization of modified nucleosides holds the potential to transform the management of a wide range of human illnesses. Modified nucleosides and their role directly led to the 2023 Nobel prize. Acyclic nucleosides, due to their distinctive physiochemical and biological characteristics, rank among the most adaptable modified nucleosides in the field of medicinal chemistry. Acyclic nucleosides are more resistant to chemical and biological deterioration, and their adaptable acyclic structure makes it possible for them to interact with various enzymes. A phosphonate group, which is linked via an aliphatic functionality to a purine or a pyrimidine base, distinguishes acyclic nucleoside phosphonates (ANPs) from other nucleotide analogs. Acyclic nucleosides and their derivatives have demonstrated various biological activities such as anti-viral, anti-bacterial, anti-cancer, anti-microbial, etc. Ganciclovir, Famciclovir, and Penciclovir are the acyclic nucleoside-based drugs approved by FDA for the treatment of various diseases. Thus, acyclic nucleosides are extremely useful for generating a variety of unique bioactive chemicals. Their biological activities as well as selectivity is significantly influenced by the stereochemistry of the acyclic nucleosides because chiral acyclic nucleosides have drawn a lot of interest due to their intriguing biological functions and potential as medicines. For example, tenofovir's (R) enantiomer is roughly 50 times more potent against HIV than its (S) counterpart. We can confidently state, "The most promising developments are yet to come in the realm of acyclic nucleosides!" Herein, we have covered the most current developments in the field of chemical synthesis and therapeutic applications of acyclic nucleosides based upon our continued interest and activity in this field since mid-1990's.
DNA 通常被称为“生命的分子”，因为它包含了地球上所有生物的遗传指令。修饰核苷的利用有可能改变多种人类疾病的管理方式。修饰核苷及其作用直接导致了 2023 年诺贝尔生理学或医学奖的产生。无环核苷由于其独特的物理化学和生物学特性，是药物化学领域最具适应性的修饰核苷之一。无环核苷更能抵抗化学和生物降解，其适应性的无环结构使其能够与各种酶相互作用。无环核苷磷酸酯 (ANPs) 与其他核苷酸类似物的区别在于，其磷酸基通过脂族官能团与嘌呤或嘧啶碱基相连。无环核苷及其衍生物表现出多种生物活性，如抗病毒、抗细菌、抗癌、抗微生物等。已被 FDA 批准用于治疗各种疾病的无环核苷类药物有更昔洛韦、泛昔洛韦和喷昔洛韦。因此，无环核苷对于生成各种独特的生物活性化合物非常有用。由于手性无环核苷具有引人入胜的生物学功能和作为药物的潜力，因此其生物活性和选择性受到无环核苷立体化学的显著影响。例如，替诺福韦的（R）对映体对 HIV 的效力大约是其（S）对映体的 50 倍。我们可以自信地说，“无环核苷领域最有前途的发展还在后面！”本文综述了自 20 世纪 90 年代中期以来我们对该领域持续的兴趣和研究活动以来，无环核苷在化学合成和治疗应用方面的最新进展。
