Novel Levoglucosenone Derivatives: Preclinical Evaluation in Breast Cancer Models.

Abstract

Levoglucosenone is a versatile chiral scaffold that has attracted growing interest for the design of structurally diverse bioactive molecules with potential therapeutic value. In this study, we explored the antitumor activity of three levoglucosenone-based derivatives in preclinical breast cancer models. In vitro, all the derivatives showed strong antiproliferative effects, induced apoptosis, and disrupted key processes involved in tumor progression, including cell adhesion, migration, and ERK/MAPK signaling. Moreover, combination with glycolysis inhibitors significantly enhanced the antitumor efficacy of these derivatives, indicating a promising synergistic effect. In vivo studies using BALB/c mice demonstrated that two of the derivatives significantly inhibited tumor growth and metastatic dissemination without evidence of systemic toxicity. Notably, combination treatments further enhanced the antitumor effects, supporting the therapeutic potential of this strategy. Overall, these findings support the pharmacological potential of levoglucosenone-based compounds and provide a basis for further medicinal chemistry optimization and preclinical investigation of their antitumor activity.