Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents.

ABSTRACT: The Warburg effect, a unique glycolytic phenomenon in cancer cells, presents a promising target for developing selective anticancer agents. Previously, BH10, a hit compound disrupting glycolytic metabolism, was identified via phenotypic screening, with Kelch-like ECH-associated protein 1 (Keap1) proposed as a potential target. To enhance its potency and selectivity, a library of BH10-derived salt compounds was synthesized. Among these, 7b exhibited nanomolar anticancer activity (IC₅₀ = 22.97 nM) and a high selectivity ratio (IC₅₀ of non-cancerous cells/IC₅₀ of cancer cells = 41.43). Molecular docking revealed that all naphthoimidazole salt analogues (7a-f) bind to Keap1 via carbonyl-mediated interactions, with variations i

SUBMITTER: Cheng Y 

PROVIDER: S-EPMC12073298 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature