Dual-Targeting Antiproliferation Hybrids Derived from 1‑Deoxynojirimycin and Kaempferol Induce MCF‑7 Cell Apoptosis through the Mitochondria-Mediated Pathway

1-Deoxynojirimycin, an α-glucosidase inhibitor, possesses various biological activities such as antitumor, antidiabetic, and antiviral effects. However, the application of 1-deoxynojirimycin is restricted by its poor lipophilicity and low bioavailability. In this study, three 1-deoxynojirimycin derivatives (8–10) comprising 1-deoxynojirimycin and kaempferol were designed and synthesized to modify their pharmacokinetics and improve their antitumor efficacy. Among them, compound 10, a conjugate of 1-deoxynojirimycin and kaempferol linked through an undecane chain, exhibited excellent lipophilicity, antiproliferative effects, and α-glucosidase inhibitory activity. Compared with 1-deoxynojirimycin, kaempferol, and their combination, compound 10 downregulated cyclooxygenase-2 (COX-2) expression, arrested the cell cycle at the S phase, induced cellular apoptosis, and inhibited the migration of MCF-7 cells. Moreover, further investigation indicated that compound 10 induced MCF-7 cell apoptosis through a mitochondrial-mediated pathway via the loss of mitochondrial membrane potential. This led to increasing intracellular levels of reactive oxygen species (ROS) and Ca2+, the downregulation of Bcl-2 expression, and the upregulation of Bax levels.