Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds.

Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer's disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound showed concentration- and time-dependent radical scavenging activity. Additionally, compounds and showed high activity in the melanoma and ovarian cancer cell lines, with LD values below 9.2 µM. Interestingly, in the AChEI test, compound showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10 cm/s). Molecular dynamics simulations of the aspirin derivatives ( and ) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as , might become very promising candidates to treat both cancer and AD.