In this article Xiaoyan Duan and coworkers screened alkaloids for inhibition of Breast cancer resistance protein (BCRP). BCRP, an ABC transporter, is associated with multidrug resistance in cancer cells due to its ability to efflux cytotoxic compounds and the fact that it has been shown to be highly expressed in cancerous cells. This makes inhibition of this protein an attractive target to help with drug resistant cancer.

In this study the authors investigated the inhibitory effects of 130 alkaloids on BCRP. They first evaluated inhibitory activity using an MTT cell viability assay in BCRP-MDCK cells, identifying eight alkaloids that exhibited significant inhibition (>50%). These assays were followed by molecular docking studies of the Alkaloids to BCRP using Discovery Studio, specifically they used CDOCKER for the docking. The docking results indicated that all eight alkaloids interact with BCRP primarily through π–π stacking or π–alkyl interactions with Phe439, as well as π–alkyl interactions with Val546. Subsequently, a common-feature pharmacophore model was developed, also using Discovery Studio, revealing that aromatic rings and hydrophobic groups are key structural features underlying BCRP inhibition.

The findings of this study provide valuable information to develop highly efficient alkaloids to inhibit BCRP to reverse MDR in cancer treatment. The full article can be found as: Chem. Res. Toxicol. 2025, 38, 9, 1595–1610.