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

Astrain-Redin, Nora and Talavera, Irene and Moreno, Esther and Ramírez, María J. and Martínez-Sáez, Nuria and Encío, Ignacio and Sharma, Arun K. and Sanmartín, Carmen and Plano, Daniel (2023) Seleno-Analogs of Scaffolds Resembling Natural Products a Novel Warhead toward Dual Compounds. Antioxidants, 12 (1). p. 139. ISSN 2076-3921

[thumbnail of antioxidants-12-00139.pdf] Text
antioxidants-12-00139.pdf - Published Version

Download (4MB)

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.

Item Type: Article
Subjects: Science Global Plos > Agricultural and Food Science
Depositing User: Unnamed user with email support@science.globalplos.com
Date Deposited: 16 Dec 2023 04:28
Last Modified: 16 Dec 2023 04:28
URI: http://ebooks.manu2sent.com/id/eprint/2389

Actions (login required)

View Item
View Item