Year: 2025
Type: article
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).
Source: Molecules
Institution: UNSW Sydney
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $3,258
Funder: Cancer Institute NSW
Awards: G3819162055, G917569198
OpenAlex ID: W4409894356