Synthesis and biological evaluation of ursolic acid-triazolyl derivatives as potential anti-cancer agents

•A novel series of C-28 ursolic acid-triazolyl derivatives has been synthesized.•Huisgen [3 + 2] cycloaddition reaction was employed for the purpose.•All the compounds were evaluated in vitro against four cancer cell lines.•Some of the compounds exhibited better anti-cancer activity than UA, 5-FU & mito-C.

A series of ursolic acid-1-phenyl-1H-[1,2,3]triazol-4-ylmethylester congeners have been designed and synthesized in an attempt to develop potent antitumor agents. A regioselective approach using Huisgen 1,3-dipolar cycloaddition reaction of ursolic acid-alkyne derivative with various aromatic azides was employed to target an array of triazolyl derivatives in an efficient manner. Their structures were confirmed by using 1H NMR, 13C NMR, IR and MS analysis. All the compounds were evaluated for anti-cancer activity against a panel of four human cancer cell lines including A-549 (lung), MCF-7 (breast), HCT-116 (colon), THP-1 (leukemia) and a normal human epithelial cell line (FR-2) using sulforhodamine-B assay. The pharmacological results showed that most of the compounds displayed high level of antitumor activities against the tested cancer cell lines compared with ursolic acid. Compounds 7b, 7g, 7p and 7r were found to be the most potent compounds in this study.

Graphical abstractA series of ursolic acid-triazolyl derivatives have been synthesized by employing click chemistry. Most of the derivatives exhibited better anti-cancer potential in vitro compared to positive controls used in the study.Figure optionsDownload full-size imageDownload as PowerPoint slide