Comprehensive review on natural pharmacophore tethered 1,2,3‐triazoles as active pharmaceuticals

Abstract

The privileged 1,2,3‐triazole scaffold is drawing researcher's attention due to its widespread applications in diverse fields such as drug discovery (e.g., carboxyamidotriazole), organic synthesis (click‐reaction template), polymeric materials (e.g., triazolamer), supramolecular receptors (e.g., triazolophane), fluorescent materials (e.g., metal–organic frameworks), and agricultural sectors (e.g., fungicides). Various 1,2,3‐triazole persuasion modules are also currently available in the market that have multiple assets such as active pharmaceuticals and agricultural purposes. Owed to the highly consistent and firmest synthesis approach, that is, click reaction of various azides and acetylene derivatives by copper (I)‐catalyzed 1,3‐dipolar cycloaddition (CuAAC), highly functionalized 1,2,3‐triazoles are prepared in scalar yields for drug discovery. Given the importance of 1,2,3‐triazole chemistry, the present review focuses specifically on the synthesis of structurally diverse 1,2,3‐triazoles linked to natural pharmacophores and their biological importance. Furthermore, the dual/multi‐pharmacophores assimilated 1,2,3‐triazoles have listed interesting biological activities that could be valuable as future drug leads. In addition, this comprehensive review can serve as a template for the development of new diverse scaffolds that will ensure for new therapeutic approaches for the existing myriad diseases and disorders.

Stereoselective Approach to Hydroxyalkyl-1,2,3-triazoles Containing Cyclooctane Core and Their Use for CuAAC Catalysis

“…The change in the solvent led to the decrease in conversion compared to the one in DCM (entries 9,11,13,15,17), and heating the reaction mixture in most cases resulted in decomposition of the organic material (entries 3,5,6,10,14,16). The attempts to perform the reaction without catalyst under conventional heating led to the very slow conversion of azide 2 into triazole 3 (entries [20][21][22]; microwave activation for 1 h did not promoted the cycloaddition (entry 23). Up to today, a number of preparative modifications of CuAAC reactions have been elaborated [1,2,47] and the use of diverse sources of catalytically active Cu(I) was reported, including Cu(I)-complex salt, Cu(I)-containing dendrimers, Cu-nanoparticles, and other molecular frameworks [48].…”

“…The change in the solvent led to the decrease in conversion compared to the one in DCM (entries 9,11,13,15,17), and heating the reaction mixture in most cases resulted in decomposition of the organic material (entries 3,5,6,10,14,16). The attempts to perform the reaction without catalyst under conventional heating led to the very slow conversion of azide 2 into triazole 3 (entries [20][21][22]; microwave activation for 1 h did not promoted the cycloaddition (entry 23). Isomeric azidoalcohol 2b was involved in the cycloaddition with phenylacetylene in the catalytic conditions to yield triazole 4 (Scheme 2).…”

“…1,2,3-Triazole represents a unique heterocycle that combines availability via straightforward and reliable synthetic approaches, based on copper-catalyzed azide-alkyne cycloaddition (CuAAC) [1][2][3] with tolerance of physiologic conditions and the properties of bioisostere of amide and ester bonds [4]. Altogether, it derives an undiminishing interest to 1,2,3-triazole as valuable scaffold for drug design [5][6][7][8][9][10][11], in particular, as a convenient and stable linker for the connection of pharmacophore fragments [12][13][14][15][16][17] and for the derivatization of natural products [18][19][20][21], as well as for the construction of peptidomimetics [22] and bioorthogonal labeling [23]. Several compounds containing 1,2,3-triazoles were approved as medicinal drugs (see, for example, Figure 1), and a much larger number of molecules with pronounced biological activity have been designed [3,10].…”

Synthesis of chiral Cu(II) complexes from pro-chiral Schiff base ligand and investigation of their catalytic activity in the asymmetric synthesis of 1,2,3-triazoles

“…The extensive biological activities of 1,2,3-triazoles (such as antibacterial characteristics, anti-inflammatory, and anticancer properties) have introduced them as an important category of synthons and building blocks in medicinal chemistry and pharmaceutical science 32 – 36 . The biological evaluation demonstrated that introducing chiral triazole cores in the scaffold of biological materials may allow greater results in enantioselective bioactivity 37 , 38 .…”

1,2,3-Triazoles and their metal chelates with antimicrobial activity

“…A vast amount of experimentation and literature reports on novel antimicrobial 1,2,3-triazoles has been accumulated over the years and the pace of research efforts seems to only accelerate. For example,’s sake, the authors of this article present several very detailed reviews on antimicrobial triazoles, published just over the past few years ( Zhang, 2019 ; Xu, 2020 ; Deng et al, 2022 ; Li and Zhang, 2022 ; Rammohan et al, 2023 ). Transition metals have played a part in medicine for millenia now.…”