Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents
The Warburg effect, a unique glycolytic phenomenon in cancer cells, presents a promising target for developing selective anticancer agents. Previously, <b>BH10</b>, a hit compound disrupting glycolytic metabolism, was identified via phenotypic screening, with Kelch-like ECH-associated pr...
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2025-04-01
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| author | Yao Cheng Tsz Tin Yu Ellen M. Olzomer Kyle L. Hoehn Frances L. Byrne Naresh Kumar David StC Black |
| author_facet | Yao Cheng Tsz Tin Yu Ellen M. Olzomer Kyle L. Hoehn Frances L. Byrne Naresh Kumar David StC Black |
| author_sort | Yao Cheng |
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| description | The Warburg effect, a unique glycolytic phenomenon in cancer cells, presents a promising target for developing selective anticancer agents. Previously, <b>BH10</b>, 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 <b>BH10</b>-derived salt compounds was synthesized. Among these, <b>7b</b> exhibited nanomolar anticancer activity (IC<sub>50</sub> = 22.97 nM) and a high selectivity ratio (IC<sub>50</sub> of non-cancerous cells/IC<sub>50</sub> of cancer cells = 41.43). Molecular docking revealed that all naphthoimidazole salt analogues (<b>7a</b>–<b>f</b>) bind to Keap1 via carbonyl-mediated interactions, with variations in hydrogen-bonding residues (e.g., VAL606, ILE559). |
| format | Article |
| id | doaj-art-9c37402a143d4683a6441583d92d8ffa |
| institution | OA Journals |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-04-01 |
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| series | Molecules |
| spelling | doaj-art-9c37402a143d4683a6441583d92d8ffa2025-08-20T01:50:45ZengMDPI AGMolecules1420-30492025-04-01309193810.3390/molecules30091938Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer AgentsYao Cheng0Tsz Tin Yu1Ellen M. Olzomer2Kyle L. Hoehn3Frances L. Byrne4Naresh Kumar5David StC Black6School of Chemistry, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, University of New South Wales, Sydney, NSW 2052, AustraliaThe Warburg effect, a unique glycolytic phenomenon in cancer cells, presents a promising target for developing selective anticancer agents. Previously, <b>BH10</b>, 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 <b>BH10</b>-derived salt compounds was synthesized. Among these, <b>7b</b> exhibited nanomolar anticancer activity (IC<sub>50</sub> = 22.97 nM) and a high selectivity ratio (IC<sub>50</sub> of non-cancerous cells/IC<sub>50</sub> of cancer cells = 41.43). Molecular docking revealed that all naphthoimidazole salt analogues (<b>7a</b>–<b>f</b>) bind to Keap1 via carbonyl-mediated interactions, with variations in hydrogen-bonding residues (e.g., VAL606, ILE559).https://www.mdpi.com/1420-3049/30/9/1938naphthoimidazoleanticancerglycolysisselectivity |
| spellingShingle | Yao Cheng Tsz Tin Yu Ellen M. Olzomer Kyle L. Hoehn Frances L. Byrne Naresh Kumar David StC Black Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents Molecules naphthoimidazole anticancer glycolysis selectivity |
| title | Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents |
| title_full | Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents |
| title_fullStr | Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents |
| title_full_unstemmed | Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents |
| title_short | Design, Synthesis, and Biological Evaluation of Naphthoquinone Salts as Anticancer Agents |
| title_sort | design synthesis and biological evaluation of naphthoquinone salts as anticancer agents |
| topic | naphthoimidazole anticancer glycolysis selectivity |
| url | https://www.mdpi.com/1420-3049/30/9/1938 |
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