Inhibitory Effects of B-, C-, and E-Ring-Truncated Deguelin Derivatives Against A549, HCT116, and MCF-7 Cancer Cells

Deguelin has been extensively studied for its anticancer properties; however, its clinical application has been hindered by concerns about in vivo toxicity. Structural modifications of deguelin including ring truncation have been explored to enhance its pharmacological properties. In this study, the design and straightforward synthesis of a series of B, C, and E (BCE)-ring-truncated deguelin analogues with deoxybenzoin backbone were described. The structure-activity relationships (SARs) were established by evaluation of their inhibitory activities against three cancer cell lines, A549 (adenocarcinomic human alveolar basal epithelial cells), HCT116 (human colorectal cancer cells), and MCF-7 (breast cancer cells). Six derivatives demonstrated significant and selective inhibitory activities. The ketone derivative 3a showed potency against A549 (IC50 = 6.62 mu M) while the oxime analogue 6a and D-ring-benzylated ketone analogue 8d exhibited activity against HCT116 (IC50 = 3.43 and 6.96 mu M, respectively). Moreover, the D-ring alkylated derivatives 8c and 8e-f were active against MCF-7 cells (IC50 < 10 mu M). The potential suitability of the BCE-ring-truncated deguelin derivatives for drug development was further supported by the favorable in silico prediction of their physicochemical properties, druglikeness, and toxicity. This study could provide valuable insights for the further development of novel anticancer agents.

Automated summary

This study describes the design and synthesis of a series of BCE-ring-truncated Deguelin analogues, which exhibit significant anticancer activity and favorable in silico predictions for physicochemical properties, druglikeness, and toxicity. These findings provide valuable insights for the further development of novel anticancer agents.