Based on previous studies, a series of 66 novel 2-phenyl-4H-chromone derivatives incorporating amide and 1,3,4-oxadiazole moieties were designed and synthesized as potential telomerase inhibitors. The results demonstrated that the majority of these compounds exhibited significant inhibitory activity against telomerase. Among them, several compounds displayed particularly potent inhibition with IC50 values below 1 μM, substantially surpassing the reference compound staurosporine (IC50 = 6.41 μM). Clear structure-activity relationships (SARs) were established, indicating that the presence and position of methoxy groups, as well as the type and number of substituents on the phenyl ring, profoundly influenced telomerase activity. Notably, compound A33 emerged as a highly effective inhibitor with strong telomerase suppressive effects.97-77-8 Formula
Flow cytometric analysis revealed that compound A33 induced cell cycle arrest at the G2/M phase in MGC-803 cells in a concentration-dependent manner, while also promoting apoptosis.49763-96-4 Molecular Weight Western blotting further confirmed that this compound significantly reduced the expression of dyskerin, a critical component of the telomerase complex responsible for its stability and functionality. These findings suggest that compound A33 exerts its anticancer effects through multiple mechanisms, including cell cycle disruption and induction of apoptotic pathways.PMID:29489226
The design strategy focused on modifying the core 2-phenyl-4H-chromone scaffold by introducing an amide linker and a 1,3,4-oxadiazole heterocycle, followed by systematic variation of substituents on the phenyl ring. This approach enabled the identification of key structural features essential for high telomerase inhibitory potency. The inclusion of electron-withdrawing groups such as halogens and trifluoromethyl at the para position of the phenyl ring enhanced activity, while substitution with aromatic fused rings or heterocycles like styryl further improved potency. Compound A33, featuring a styryl group, stood out not only for its strong telomerase inhibition but also for its moderate yet broad-spectrum antiproliferative activity across multiple human cancer cell lines.
Importantly, compound A33 showed minimal toxicity toward normal human liver cells (L-02), with an IC50 value of 2.21 μM, indicating excellent selectivity for tumor cells over normal somatic cells. This favorable safety profile, combined with its multifaceted biological activities, positions A33 as a promising lead candidate for further development into targeted anticancer therapeutics. Overall, these results underscore the potential of rational molecular design in generating potent telomerase inhibitors with therapeutic relevance.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