Developmental and angiogenic safety profiles of novel pyridine-based chalcone

Introduction: Pyridine chalcone derivatives are emerging anticancer candidates with potent activity against different types of cancer. However, their developmental and angiogenic safety profiles remain unexplored. In our lab, we recently generated a series of novel pyridine-based chalcone analogs; we reported that two of them, OH17 and OH25, are highly effective against different types of cancer cell models. Methods: evaluation using normal embryonic fibroblast cells (NEFCs). Results: Our data revealed that both OH17 and OH25 did not affect the normal development of the embryos and their survival rate when they were exposed to these two compounds at 3 days of incubation. Meanwhile, the CAM analysis showed no significant alterations in vessel area, branching, or density, with only a minor reduction in average vessel length. More significantly, gene expression patterns of apoptotic and angiogenic key markers remain unchanged across different tissues from several organs of exposed embryos. Consistently, NEFCs retained normal viability and fibroblast morphology following treatment with the two compounds. Discussion: Together, these findings, combined with our previous reports, demonstrate OH17 and OH25 safety in addition to their potent anticancer activity. Thus, paving the way towards a favorable therapeutic window for these two compounds in support of their further development as promising anticancer agents.