Click chemistry-assisted synthesis of novel C-2 triazole-linked betulinic acid conjugates with azidothymidine as potential anti-HIV agents

Abstract

A new synthetic approach to C-2 triazole-linked bioconjugates of lupane triterpenoids with 3'-azido-3'deoxythymidine (AZT) based on Cu I -catalyzed 1,3-cycloaddition between alkynes and azides is described. The proposed strategy towards AZT-betulinic acid hybrid molecules as potential anti-HIV agents makes it possible to vary the C-3 and C-28 pharmacophores in triterpene moieties. The C-2 propargyl-substituted betulinic acid and its mono-or bi-functional derivatives with side chain at C-3 and/or C-28 positions were successfully synthesized by employing the click reaction.

Synthesis of novel 1,2,3-triazole-based hybrids via click reactions

“…To increase the structural range of the obtained compounds containing a triple bond, we also synthesized thiopropargyl-1,2,4-triazoles 12 from the corresponding 5-aryl-4-phenyl-4H-1,2,4-triazole-3-thiols 11 35 (Scheme 5), which, as mentioned above, have been shown to be physiologically active substances. Finally, the desired hybrid compounds were prepared by a Cu-catalyzed azide-alkyne click reaction [14][15][16] between the propargylated compounds 10/12 and azido derivatives 3, 5 and 8 (Scheme 6). As reductant, ascorbic acid was used in most of the syntheses of the triazole derivatives 13-17, which were obtained in moderate/high yields (Yields = 55-76%; Table 3).…”

“…13 The main method to prepare 1,2,3-triazoles involves the 1,3-cycloaddition of organic azides with a terminal triple bond, via a click reaction. [14][15][16] In this paper we propose the synthesis of novel triazole-linked hybrids containing biologically active fragments, with the aim to increase the structural range of known and active 1,2,3-triazole derivatives.…”

Recent advances in natural anti‐HIV triterpenoids and analogs

“…Then, a series of C‐2 triazole‐linked bioconjugates of lupane triterpenoids with AZT was synthesized based on a CuI‐catalyzed 1,3‐cycloaddition between alkynes and azides (Figure 7). The proposed strategy concerning AZT–betulinic acid hybrid molecules as potential anti‐HIV agents makes it possible to vary the C‐3 and C‐28 pharmacophores in the triterpene moieties 57 . Fourteen conjugates of 3,28‐di‐ O ‐acylbetulins with AZT were prepared and nine conjugates ( 51 – 59 ; Tables 1 and 2) exhibited potent anti‐HIV activity with EC 50 values ranging from 0.040 to 0.098 μM in HIV‐1 NL4‐3 infected MT‐4 cells 58 …”

Synthesis, Antimicrobial Activity, Molecular Docking and DFT Study: Aryl‐Carbamic Acid 1‐Benzyl‐1H‐[1,2,3]Triazol‐4‐ylmethyl Esters

“…A library of the synthesized triazoles (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18) and their alkynes (2a-c) was screened in vitro for antibacterial activity against gram (+) bacteria B. subtilis (MTCC 441), S. epidermidis (MTCC 6680), and gram (-) bacteria E. coli (MTCC 16521), P. auroginosa (MTCC 424) by standard serial dilution method using a stock solution of 100 μg mL À 1 concentration in dimethyl sulfoxide solvent. However, MTCC refer to the microbial type culture collection.…”