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Published on: February 15, 2016
Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents
Yao Cheng1, Tsz Tin Yu1, Ellen M Olzomer2
1School of Chemistry, University of New South Wales, Sydney, NSW 2052, Australia.
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 in hydrogen-bonding residues (e.g., VAL606, ILE559).
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