Sumit Kumar, Aditi Arora, Riya Chaudhary, Rajesh Kumar, Christophe Len, Monalisa Mukherjee, Brajendra K. Singh, Virinder S. Parmar
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引用次数: 0
摘要
DNA 通常被称为 "生命分子"，因为它掌握着地球上所有生物的遗传指令。利用改性核苷有望改变人类多种疾病的治疗方法。修饰核苷及其作用直接导致了 2023 年诺贝尔奖的产生。无环核苷具有独特的理化和生物学特性，是药物化学领域适应性最强的修饰核苷之一。无环核苷具有更强的抗化学和生物劣化能力，其适应性强的无环结构使其能够与各种酶相互作用。膦酸基通过脂肪族官能团与嘌呤或嘧啶碱基相连，是无环核苷膦酸盐（ANPs）与其他核苷酸类似物的区别所在。无环核苷及其衍生物具有多种生物活性，如抗病毒、抗菌、抗癌、抗微生物等。更昔洛韦（Ganciclovir）、泛昔洛韦（Famciclovir）和喷昔洛韦（Penciclovir）是 FDA 批准用于治疗各种疾病的无环核苷类药物。因此，无环核苷在生成各种独特的生物活性化学物质方面非常有用。无环核苷的立体化学对其生物活性和选择性有很大影响，因为手性无环核苷具有引人入胜的生物功能和作为药物的潜力，因此引起了广泛的兴趣。例如，替诺福韦的对映体（R）对艾滋病病毒的药效大约是其对映体（S）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！"自 1990 年代中期以来，我们一直关注无环核苷的化学合成和治疗应用领域，并在此基础上介绍了这一领域的最新进展。
Recent Advances in the Synthesis of Acyclic Nucleosides and Their Therapeutic Applications
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.
期刊介绍：
Topics in Current Chemistry provides in-depth analyses and forward-thinking perspectives on the latest advancements in chemical research. This renowned journal encompasses various domains within chemical science and their intersections with biology, medicine, physics, and materials science.
Each collection within the journal aims to offer a comprehensive understanding, accessible to both academic and industrial readers, of emerging research in an area that captivates a broader scientific community.
In essence, Topics in Current Chemistry illuminates cutting-edge chemical research, fosters interdisciplinary collaboration, and facilitates knowledge-sharing among diverse scientific audiences.
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