Synthesis and Bioactivity Assessment of <i>N</i>-Aryl-Azasesamins

Sesamin, a tetrahydrofuran lignan, has gained significant attention over the past few decades due to its versatile medicinal activities. However, until now, the research on sesamin analogues has not been explored extensively. In this study, a series of new <i>N</i>-aryl-azasesamins were...

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Main Authors: Jiri Wu, Xubing Qi, Yogini S. Jaiswal, Cui Lin, Xun Song, Xinrong Xie, Shaoyang Su, Yifu Guan, Leonard L. Williams, Hedong Bian
Format: Article
Language:English
Published: MDPI AG 2024-10-01
Series:Chemistry
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Online Access:https://www.mdpi.com/2624-8549/6/6/79
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Summary:Sesamin, a tetrahydrofuran lignan, has gained significant attention over the past few decades due to its versatile medicinal activities. However, until now, the research on sesamin analogues has not been explored extensively. In this study, a series of new <i>N</i>-aryl-azasesamins were synthesized for the first time using sesamin as a raw material. The mechanism of the key breakage of the ethereal bond of the tetrahydrofuran ring in sesamin has been studied. The configuration of C6 in <i>N</i>-aryl-azasesamins was confirmed through NMR and X-ray single crystal refraction analyses. The results showed that the configuration of <i>N</i>-aryl-azasesamins was opposite to sesamin in C6. Subsequently, the <i>N</i>-aryl-azasesamins were evaluated for their antifungal and antitumor activities via micro-broth dilution and MTT assays. It was observed that none of the <i>N</i>-aryl-azasesamins exhibited inhibitory activity against the growth of <i>C. albicans</i> and <i>C. neoformans</i> at a concentration of 100 μg/mL. Most analogues showed no activity against HepG2 cells. However, <b>21c</b> and <b>21k</b> demonstrated antitumor activity after 24 h of incubation with IC<sub>50</sub> values of 6.49 μM and 4.73 μM, respectively. These results suggest that some <i>N</i>-aryl-azasesamins exhibit significantly enhanced antitumor activity compared with sesamin.
ISSN:2624-8549