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

Abstract

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.

Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors

“…The synthesis procedure and the characterisation of the compounds were described in our previous study. 30 Briefly, hydrogen sodium selenide (NaHSe) was formed by the reduction of elemental Se with NaBH 4 in water. Then, the corresponding acid chloride was added to the reaction mixture to form the corresponding sodium selenoate by a nucleophilic acyl substitution.…”

“…Reagents and conditions: (i) H 2 O, 20 min, and room temperature; (ii) THF/H 2 O, 60 min, and room temperature; (iii) ClCOCOCl, CH 2 Cl 2 , 12 h, and room temperature; (iv) BrCH 2 CH = CH 2 or BrCH 2 C≡CH, THF/H 2 O, 90 min, and room temperature. 30 …”

“…The studied compounds 1a–19a and 1b–19b were synthesised in our previous work 30 and their chemical structures are depicted in Figure 1 .…”

Design, synthesis, and biological evaluation of novel quinoxaline aryl ethers as anticancer agents

“…Apoptosis tests were conducted using the Muse Annexin V/7‐AAD and Caspase 3/7‐7‐AAD kit from EMD Millipore, Darmstadt, Germany, following the provided protocol as described in Astrain‐Redin et al. (2023). The cells were initially seeded in a 6‐well plate at a density of 1 × 10 5 cells/well.…”

Selenization of Small Molecule Drugs: A New Player on the Board

“…Nonetheless, a multitude of compelling studies have reported that they can act only for limited periods and present a risk of harmful side effects. To overcome these drawbacks, researchers are eager to find and develop innovative candidates to combat this disorder. − In this line, burgeoning evidence revealed that a wide range of selenocompounds has great effectiveness in AD. − …”