Self-Assembled Glycosylated Chalcone–Boronic Acid Nanodrug Exhibits Anticancer Activity through Mitochondrial Impairment

Abstract

Chalcone and boronic acids are important privileged structures in myriads of natural and synthetic products having diverse biological activities. However, their therapeutic window is highly narrow due to their hydrophobic nature affecting unpredictable biodistribution. To address this, we herein have synthesized a novel hybrid glycosylated chalcone–boronic acid library. Cell viability, flow cytometry, confocal microscopy, and gel electrophoresis assays demonstrated that one of the library members induces cell cycle arrest in the G2/M phase through the activation of p21 and decrease levels of cyclin B1 and CDK1. In addition, it also induces apoptosis, primarily due to the inhibition of Bcl-2/Bcl-xl and the augmentation of BAX to prompt mitochondrial damage and reactive oxygen species generation. Most interestingly, the lead cytotoxic glycosylated chalcone–boronic acid self-assembled in water into a spherical nanodrug that can further entrap another anticancer drug (doxorubicin) to show remarkably improved efficacy in breast cancer cells. This novel lead compound has prospective as a vector-free nanodrug for combination cancer therapy.