Selenourea derivatives as candidates for the treatment of Alzheimer’s disease: Promising in vivo results in a Caenorhabditis elegans model

Alzheimer’s disease (AD) is a neurodegenerative disorder that affects millions of people worldwide every year. There is a need to search for new drug candidates to help minimize the impact of the disease, such as selenium compounds. Selenium compounds are promising candidates for the treatment of neurodegenerative diseases due to their biological properties. Some classes have shown promising effects in previous in vivo studies using amyloid-beta aggregation models, however, selenourea derivatives have not been evaluated in this context. The objective of this study was to evaluate the safety and pharmacological effects of selenourea compounds in reducing paralysis rates and increasing longevity in an amyloid aggregation model, as well as to predict their in silico ADMET properties. For this purpose, transgenic CL2006 [pCL12 (unc-54/human Abeta peptide 1–42 minigene) + pRF4] worms were subjected to acute treatment, for 30 min, at the L1 larval stage, with the selenourea derivative compounds FA212, FA213, FA215, FA220, and FA221 at concentrations of 5 to 200 µM. 48 h after the end of treatment, survival, paralysis, and longevity assays were carried out. When the worms reached the L4 stage, we analyzed the survival assay and observed that the compounds FA213 and FA221 demonstrated toxicity at the highest concentrations tested (both present a m-metoxy group in their structure). Additionally, the pharmacological properties of the main compound were predicted by using ADMET predictor software. All selenourea compounds, with the exception of FA213, significantly reduced the rate of paralysis in the worms, especially FA215 and FA221, which improved the phenotype in all tested concentrations. Both compounds present a p-methoxy group in their structure. FA220, which presents a p-methyl group in the phenyl ring, improved Aβ-induced paralysis and extended the longevity of these worms. This study was the first to evaluate the efficacy of these selenourea compounds in attenuating the locomotor dysfunction caused by Aβ aggregation in C. elegans. The results demonstrated promising effects of the compound FA220 as a candidate for further investigation in Alzheimer’s disease models, due to its low toxicity and its ability to delay paralysis and extend the lifespan of worms.