Effects of 1<i>H</i>-1,2,3-Triazole Derivatives of 3-<i>O</i>-Acetyl-11-Keto-Beta-Boswellic Acid from <i>Boswellia sacra</i> Resin on T-Cell Proliferation and Activation

<b>Background:</b> 3-<i>O</i>-acetyl-11-keto-<i>β</i>-boswellic acid (<i>β</i>-AKBA), a triterpene natural product, is one of the main natural products of <i>Boswellia sacra</i> resin (BSR) and has reported biological and immunomodulatory e...

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Main Authors: Abdo Meyiah, Satya Kumar Avula, Ahmed Al-Harrasi, Eyad Elkord
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Pharmaceuticals
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Online Access:https://www.mdpi.com/1424-8247/17/12/1650
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Summary:<b>Background:</b> 3-<i>O</i>-acetyl-11-keto-<i>β</i>-boswellic acid (<i>β</i>-AKBA), a triterpene natural product, is one of the main natural products of <i>Boswellia sacra</i> resin (BSR) and has reported biological and immunomodulatory effects. 1<i>H</i>-1,2,3-triazole derivatives of <i>β</i>-AKBA (named <b>6a</b>–<b>6d</b>) were synthesized from <i>β</i>-AKBA. The 1<i>H</i>-1,2,3-triazole compounds are also known to have a wide range of biological and pharmacological properties as demonstrated by in vitro and in vivo studies. This study aimed to investigate the effects of these 1<i>H</i>-1,2,3-triazole derivatives of <i>β</i>-AKBA on human T-cell proliferation and activation. <b>Methods:</b> PBMCs isolated from healthy donors were activated by anti-CD3/CD28 monoclonal antibodies in the presence of <i>β</i>-AKBA (<b>1</b>) or 1<i>H</i>-1,2,3-triazole derivatives of <i>β</i>-AKBA or DMSO controls. <b>Results:</b> We found that similar to the parent compound <i>β</i>-AKBA (<b>1</b>), derivatives <b>6a</b>, <b>6b</b>, and <b>6d</b> significantly inhibited T-cell expansion/proliferation and reduced the levels of CD25 activation marker on CD4<sup>+</sup> and CD8<sup>+</sup> T cells without exerting significant cytotoxic effects on T-cell viability at a concentration of 25 µM. However, compound <b>6c</b> further inhibited T-cell expansion/proliferation and CD25 expression, but had a significant cytotoxic effect on cell viability at similar concentrations of 25 µM. <b>Conclusions:</b> These findings demonstrate the immunoinhibitory effects of <i>β</i>-AKBA (<b>1</b>) and its corresponding triazole derivatives on T-cell proliferation and activation, highlighting the promising therapeutic potential of these compounds in T-cell-mediated diseases.
ISSN:1424-8247