| Autor: |
Choithramani, Asmita, Das, Rudradip, Bothra, Gourav, Patel Vatsa, Priyanka, Muthukumar, Venkatesh, Bhuvana, Bombothu Kavya Sai, Kapoor, Saumya, Moola, Deepshika, Chowdhury, Moumita Ghosh, Mandoli, Amit, Shard, Amit |
| Zdroj: |
MedChemComm; 2024, Vol. 15 Issue: 8 p2729-2744, 16p |
| Abstrakt: |
Oral cancer (OC) stands as a prominent cause of global mortality. Despite numerous efforts in recent decades, the efficacy of novel therapies to extend the lifespan of OC patients remains disappointingly low. Consequently, the demand for innovative therapeutic agents has become all the more pressing. In this context, we present our work on the design and synthesis of twenty-five novel quinoxaline-tethered imidazopyri(mi)dine derivatives. This was followed by comprehensive investigations into the impact of these molecules on the OC cell line. The in vitrocytotoxicity studies performed in CAL-27 and normal oral epithelial (NOE) cell lines revealed that some of the synthesized molecules like 12dhave potent antiproliferative activity specifically towards OC cells with an IC50of 0.79 μM and show negligible cytotoxicity over NOE cells. Further, 12darrested cell growth in the S phase of the cell cycle and induced cell death by early apoptosis. The in silicostudies validated that 12dbinds to the activator binding site on pyruvate kinase M2 (PKM2) overexpressed in OC while the lactate dehydrogenase (LDH)-coupled enzyme assay established 12das a potent PKM2 activator with an AC50of 0.6 nM. Hence, this study provides fruitful evidence for the designed compounds as anticancer agents against OC. |
| Databáze: |
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