Compound A33, a novel 2-phenyl-4H-chromone derivative bearing a styryl-substituted 1,3,4-oxadiazole moiety, demonstrates potent telomerase inhibitory activity with an IC50 value of 0.44 μM, significantly surpassing staurosporine (IC50 = 6.41 μM) and approaching the potency of BIBR1532 (IC50 = 0.29 μM). Its anticancer effects were evaluated in human gastric cancer MGC-803 cells, where it induced cell cycle arrest at the G2/M phase in a concentration-dependent manner. Flow cytometric analysis revealed that treatment with 3, 6, and 9 μM of A33 increased the proportion of cells in G2/M from 9.76% to 55.13%, while reducing G0/G1 and S phase populations from 52.71% and 37.61% to 32.62% and 12.25%, respectively. This disruption of cell cycle progression strongly correlates with the inhibition of cellular proliferation.
Further investigation confirmed that A33 induces apoptosis in MGC-803 cells. Annexin V-FITC/PI staining showed a marked increase in apoptotic cells—rising from 4.27% in untreated controls to 11.39%, 57.31%, and 86.96% after exposure to increasing concentrations of A33 for 48 hours. The progressive shift toward early and late apoptotic populations confirms that apoptosis is a primary mechanism underlying its antiproliferative effect.85721-33-1 Formula
The molecular basis of this activity lies in the suppression of dyskerin, a core component of the telomerase holoenzyme essential for RNA stabilization and enzymatic activity.62284-79-1 MedChemExpress Western blot analysis demonstrated that A33 treatment led to a significant, dose-dependent decrease in dyskerin protein levels. Concomitantly, expression of NOP10 and NHP2—the two other components of the dyskerin-NOP10-NHP2 trimer complex—was also reduced.PMID:31194388 Since this trimer plays a critical role in telomerase assembly and function, its downregulation by A33 likely results in impaired telomerase activity, leading to telomere shortening and eventual cell death.
These findings indicate that A33 exerts its anticancer effects through a dual mechanism: direct inhibition of telomerase activity and induction of cell cycle arrest and apoptosis via dyskerin suppression. Unlike conventional chemotherapeutics that target DNA replication or microtubule dynamics, A33 targets a key regulatory node in telomere maintenance, offering a potentially more selective and durable therapeutic strategy. The compound’s low toxicity toward normal L-02 liver cells further supports its potential as a safe and effective candidate for future development in targeted cancer therapy.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com
