Selenium compounds are pivotal in medicinal chemistry for their antitumoral and antioxidant properties. Forty seven acylselenoureas have been designed and synthesized following a fragment-based approach. Different scaffolds, including carbo- and hetero-cycles, along with mono- and bi-cyclic moieties, have been linked to the selenium containing skeleton. The dose- and time-dependent radical scavenging activity for all of the compounds were assessed using the in vitro 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assays. Some of them showed a greater radical scavenging capacity at low doses and shorter times than ascorbic acid. Therefore, four compounds were evaluated to test their protective effects against H2O2-induced oxidative stress. One derivative protected cells against H2O2-induced damage, increasing cell survival by up to 3.6-fold. Additionally, in vitro cytotoxic activity of all compounds was screened against several cancer cells. Eight compounds were selected to determine their half maximal inhibitory concentration (IC50) values towards breast and lung cancer cells, along with their selectivity indexes. The breast cancer cells turned out to be much more sensitive than the lung. Two compounds (5d and 10a) stood out with IC50 values between 4.2 μM and 8.0 μM towards MCF-7 and T47D cells, with selectivity indexes greater than 22.9. In addition, compound 10b exhibited dual antioxidant and cytotoxic activities. Although further evidence is needed, the acylselenourea scaffold could be a feasible frame to develop new dual agents.

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 13a showed concentration- and time-dependent radical scavenging activity. Additionally, compounds 14a and 17a showed high activity in the melanoma and ovarian cancer cell lines, with LD50 values below 9.2 µM. Interestingly, in the AChEI test, compound 14a showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10−6 cm/s). Molecular dynamics simulations of the aspirin derivatives (14a and 14b) 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 14a, might become very promising candidates to treat both cancer and AD.

Purpose We aimed to prospectively investigate the association of an overall oxidative balance score (OBS) with all-cause death and cause-specific mortality among participants in the Seguimiento Universidad de Navarra (SUN) Study, a Mediterranean cohort of Spanish graduates. Methods Using baseline information on 12 a priori selected dietary and non-dietary lifestyle pro- and antioxidants exposures—vitamins C and E, β-carotenes, selenium, zinc, heme iron, polyphenols, total antioxidant capacity, body mass index, alcohol, smoking, and physical activity—we constructed an equally weighted OBS categorized into quartiles, with higher scores representing greater antioxidant balance. Cox proportional hazards models were fitted to evaluate the association between the OBS and mortality. Results A total of 18,561 participants (mean [SD] age, 38.5 [12.4] years; 40.8% males) were included in the analysis. During a median follow-up of 12.2 years (interquartile range 8.3–14.9), 421 deaths were identified, including 80 deaths from cardiovascular disease (CVD), 215 from cancer, and 126 from other causes. After adjustment for potential confounders, the hazard ratios and 95% confidence interval (CIs) between the highest quartile (predominance of antioxidants) vs. the lowest quartile (reference category) were 0.35 (95% CI 0.22–0.54, P-trend < 0.001) for all-cause mortality, 0.18 (95% CI 0.06–0.51, P-trend = 0.001) for CVD mortality, 0.35 (95% CI 0.19–0.65, P-trend = 0.002) for cancer mortality, and 0.45 (95% CI 0.20–1.02, P-trend = 0.054) for other-cause mortality. Conclusion Our findings suggest a strong inverse association between the OBS and all-cause, CVD, and cancer mortality. Individuals exposed to both antioxidant dietary and lifestyle factors may potentially experience the lowest mortality risk. Study registry number Dynamic Mediterranean Prospective Cohort: the SUN Project; NCT02669602. https://clinicaltrials.gov/ct2/show/NCT02669602. https://proyectosun.es

Objectives Whether oxidative balance impacts mortality risk requires accounting not only for dietary patterns but also for lifestyle exposures. We aimed to investigate the association between an overall oxidative balance with all-cause, cardiovascular, and cancer mortality risk among participants in the Seguimiento Universidad de Navarra (SUN) Study, a Mediterranean cohort of middle-aged Spanish graduate students. Methods Using baseline information from 12 a priori selected dietary and non-dietary lifestyle pro- and antioxidants exposures — vitamins C and E, betacarotenes, minerals (Se, Zn, heme-Fe), polyphenols, total antioxidant capacity, body mass index, alcohol, smoking, and physical activity — we constructed an oxidative balance score (OBS) categorized in equal-weighting quartiles, with higher scores meaning greater antioxidant balance. Cox proportional hazards models were fitted to evaluate the association between the OBS and mortality risk. Cases were ascertained through consultation of the National Death Index. Results A total of 19,083 participants (mean [SD] age, 38.5 [12.4] years; 59.2% females) were included in the analysis. During a median follow-up of 12.2 years (interquartile range, 8.1–14.9), 421 deaths were identified, including 80 cardiovascular (CV) deaths and 215 cancer deaths. After adjustment for potential confounders, the hazard ratio between the highest quartile (predominance of antioxidant) vs. the lowest quartile (reference category) was 0.43 (95% confidence interval [CI], 0.29–0.66, P-trend &lt; 0.001) for all-cause mortality; 0.19 (95% CI 0.07–0.50, P-trend = 0.012) for CV mortality; 0.47 (95% CI 0.26–0.84, P-trend = 0.012) for cancer mortality. The antioxidant balance of dietary exposures and lifestyle exposures contributed towards reducing mortality risk, however, the individual effects were smaller than the combination of both exposures, suggesting the utility of the OBS to reflect the synergistic effect between the individual components. Conclusions Our findings suggest a strong inverse association between OBS score and decreased all-cause, CV, and cancer mortality. Individuals exposed to both antioxidant dietary and lifestyle factors may potentially experience the lowest mortality risk. Funding Sources Instituto de Salud Carlos III, FEDER, Navarra Regional Government and University of Navarra.