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Volume 32, Issue 2
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Background

Oral squamous cell carcinoma (OSCC) represents the primary form of oral cancer, posing a significant global health threat. The existing chemotherapy options are accompanied by notable side effects impacting patient treatment adherence. Consequently, the exploration and development of novel substances with enhanced anticancer effects and fewer side effects have become pivotal in the realms of biological and chemical science.

Objective

This work presents the pioneering examples of naphthoquinone-coumarin hybrids as a new category of highly effective cytotoxic substances targeting oral squamous cell carcinoma (OSCC).

Methods

Given the significance of both naphthoquinones and coumarins as essential pharmacophores/privileged structures in the quest for anticancer compounds, this study focused on the synthesis and evaluation of novel naphthoquinones/coumarin hybrids against oral squamous cell carcinoma.

Results

By several , , and approaches, we demonstrated that compound was highly cytotoxic against OSCC cells and several other cancer cell types and was more selective than current chemotherapeutic drugs (carboplatin) and the naphthoquinone lapachol. Furthermore, compound was non-hemolytic and tolerated at 50 mg/kg with an LD of 62.5 mg/kg. Furthermore, compound did not induce apoptosis and cell cycle arrest but led to intracellular vesicle formation with LC3 aggregation in autophagosomes, suggesting an autophagic cell death. Additionally, had a high-affinity potential for PKM2 protein, higher than the known ligands, such as lapachol or shikonin, and was able to inhibit this enzyme activity .

Conclusion

We assert that compound shows promise as a potential lead for a novel chemotherapeutic drug targeting OSCC, with potential applicability to other cancer types.

© 2025 Bentham Science Publishers
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/content/journals/cmc/10.2174/0109298673298471240605072658
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Determination of Inhibitory Effect of PKM2 Enzyme and Antitumoral Activity of Novel Coumarin-naphthoquinone Hybrids
Curr. Med. Chem. 32, 359 (2025); https://doi.org/10.2174/0109298673298471240605072658
/content/journals/cmc/10.2174/0109298673298471240605072658
/content/journals/cmc/10.2174/0109298673298471240605072658
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  • Article Type:     Research Article
Keyword(s): chemotherapy; coumarin; naphthoquinone; oral cancer; Oral squamous cell carcinoma; pyruvate kinase M2

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