Modified Nucleosides, Nucleotides and Nucleic Acids via Click Azide-Alkyne Cycloaddition for Pharmacological Applications

Abstract

The click azide = alkyne 1,3-dipolar cycloaddition (click chemistry) has become the approach of choice for bioconjugations in medicinal chemistry, providing facile reaction conditions amenable to both small and biological molecules. Many nucleoside analogs are known for their marked impact in cancer therapy and for the treatment of virus diseases and new targeted oligonucleotides have been developed for different purposes. The click chemistry allowing the tolerated union between units with a wide diversity of functional groups represents a robust means of designing new hybrid compounds with an extraordinary diversity of applications. This review provides an overview of the most recent works related to the use of click chemistry methodology in the field of nucleosides, nucleotides and nucleic acids for pharmacological applications.

Click chemistry: A fascinating, Nobel-winning method for the improvement of biological activity

“…In addition to their application (corrosion inhibitors, photographic photoreceptors, photostabilizers of polymers, dyestuff, fluorescent whiteners, optical brighteners) in many fields in the industry [20] , 1,2,3-triazoles also steer with many successful applications in the field of pharmaceuticals and agrochemicals due to their wide biological activity capacity [21,22] . Moreover, thanks to their tolerance for typical biological conditions and almost all functional groups along with hydrogen bonding capacity based high solubility in aqueous solutions, 1,2,3triazole compounds are targeted in the synthesis of various polymeric carrier systems and dendrimers, crosslinking of micelles and the syntheses on modifying the surfaces of various nanoparticle carrier systems [23][24][25][26][27] . The stability of those compounds makes the reaction in which they are synthesized extremely ideal for bioconjugation, and so as a result, the binding of oligonucleotides, proteins, polysaccharides, viruses and bacteria such as E. coli to various substrates is successfully accomplished using this approach [28][29][30][31][32][33] .…”

Recent Advances in the Development and Synthesis of Carbohydrate‐Based Molecules with Promising Antibacterial Activity

“…This strategic insertion of the azide moiety conveniently enabled Titz and co-workers to link the sugar probe to Npropargylated ciprofloxacin 92 in a CuAAC reaction after sugar deacetylation, affording a triazole bridge in the desired compound 87. In fact, this click-chemistry approach is being increasingly used in carbohydrate chemistry applied to a vast number of therapeutic areas, gathering unanimous recognition as a rapid and facile methodology for the preparation of bioactive modified sugars, [32,99,100] carbohydrate-based dual pharmacophore drug hybrids, [101][102][103][104] organometallic glycoconjugates, [105] multivalent glycoclusters, [106,107] among others. [108][109][110] The same click-chemistry strategy was employed in the synthesis of compound 88 (Scheme 13), but having Cglycoside 83 [92] (Scheme 11) instead as the starting material.…”

Клік-Хімія Та Біоортогональні Реакції: Прорив В Епоху Функціональності В Хімії

“…Завдяки придатності для толерантного поєднання фрагментів з широким спектром функціональних груп методологія клік-хімії є надійним варіантом біокон'югації в медичній хімії, що забезпечує ефективні умови реакції за участю біомолекул, ключовими представниками яких є нуклеозиди, нуклеотиди та нуклеїнові кислоти, оскільки вони відіграють вирішальну роль у всіх функціях життєдіяльності клітини. Саме тому розроблення аналогів для різних біологічних мішеней є важливим для фармакологічних досліджень [11]. Враховуючи значення 1,2,3-триазолів як біосумісних фармакофорів та біоізостерних лінкерів, реакції CuAAC стали дуже привабливими для кон-Рис.…”