Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry

doi:10.1016/j.tetlet.2012.02.022

Tetrahedron Letters

Volume 53, Issue 15, 11 April 2012, Pages 1987-1989

https://doi.org/10.1016/j.tetlet.2012.02.022 Get rights and content

Abstract

In the present study, a new strategy to link AZT with betulin/betulinic acid (BA) by click chemistry was designed and achieved. This conjugation via a triazole linkage offers a new direction for the modification of anti-HIV triterpenes. Click chemistry provides an easy and productive way for linking two molecules, even when one of them is a large natural product. Among the newly synthesized conjugates, compounds 15 and 16 showed potent anti-HIV activity with EC₅₀ values of 0.067 and 0.10 μM, respectively, which are comparable to that of AZT (EC₅₀: 0.10 μM) in the same assay.

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Acknowledgments

This investigation was supported by Grant AI-077417 from the National Institute of Allergy and Infectious Diseases (NIAID) awarded to K.-H.L. This study was also supported in part by the Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004). Efficient purification of all the synthetic BA analogs was performed with a Grace Reveleris® flash chromatography system equipped with RevealX(TM) detection allowing for multisignal (UV/ELSD) collection to low mg

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Anti-AIDS agents 88. Anti-HIV conjugates of betulin and betulinic acid with AZT prepared via click chemistry

Abstract

Graphical abstract

Section snippets

Acknowledgments

Eur. J. Pharm. Sci.

Tetrahedron

Tetrahedron

Tetrahedron

J. Med. Chem.

Antimicrob. Agents Chemother.