Synthesis, In vitro and In silico Studies of Novel Bis‐triazolopyridopyrimidines from Curcumin Analogues as Potential Aromatase Agents

Breast cancer remains a major global health issue, particularly affecting women and contributing significantly to mortality rates. Current treatments for estrogen receptor‐positive breast cancers, such as aromatase inhibitors, are effective but often come with side effects and resistance issues. This study addresses these gaps by targeting aromatase, an enzyme crucial for estrogen synthesis, which plays a pivotal role in breast cancer progression. The innovative approach involves synthesizing novel bis‐triazolopyridopyrimidines, designed to leverage the combined pharmacological benefits of pyridopyrimidine and 1,2,4‐triazole structures, known for their potent aromatase inhibition and anti‐cancer properties. These compounds were synthesized and characterized using 1H‐NMR, 13C‐NMR, and MS spectral analyses, and their anticancer efficacy was evaluated through MTT assays against MCF‐7 breast cancer cell lines in vitro. Molecular docking analyses revealed strong binding energies with aromatase, particularly for compounds 5 b, 5 c, 10 a, and 10 b, indicating their potential as effective aromatase inhibitors. The study highlights these compounds as promising candidates for further development as therapeutic agents against breast cancer.