New resveratrol analogs as improved biologically active structures: Design, synthesis and computational modeling.

Mlakić, Milena; Odak, Ilijana; Barić, Danijela; Talić, Stanislava; Šagud, Ivana; Štefanić, Zoran; Molčanov, Krešimir; Lasić, Zlata; Kovačević, Borislav; Škorić, Irena (2024) New resveratrol analogs as improved biologically active structures: Design, synthesis and computational modeling.. Bioorganic Chemistry, 143 . ISSN 0045-2068

PDF - Accepted Version - article Restricted to Closed Access until February 2026. Available under License Creative Commons Attribution Non-commercial No Derivatives. Download (2MB) | Request a personal copy from author

Abstract

New analogs of the well-known bioactive trihydroxy-stilbene resveratrol were synthesized to investigate their potential biological activity. The focus was on assessing their ability to inhibit cholinesterase enzymes (ChEs) and their antioxidative properties, which were thoroughly examined. New resveratrol analogs were synthesized through Wittig or McMurry reaction in moderate-to-good yields. In all synthetic pathways, mixtures of cis- and trans-isomers were obtained, then separated by chromatography, and trans-isomers were isolated as targeted structures. The stilbene derivatives underwent evaluation for antioxidant activity (AOA) using DPPH and CUPRAC assay, and their potential to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was also measured. The biological tests have shown that the same compounds exhibited significant antioxidative and butyrylcholinesterase inhibitory potential, as evidenced by lower IC50 values compared to the established standards, trans-resveratrol, and galantamine, respectively. Additionally, molecular docking of the selected synthesized potential inhibitors to the enzyme's active site was performed, followed by assessing the complex stability using molecular dynamics simulation lasting 100 ns. Lastly, the new compounds underwent examination to determine their potential mutagenicity.

Item Type:	Article
Uncontrolled Keywords:	antioxidative activity; cholinesterase inhibition; computational modeling; resveratrol analogs; synthesis
Subjects:	NATURAL SCIENCES > Chemistry > Theoretical Chemistry NATURAL SCIENCES > Chemistry > Organic Chemistry NATURAL SCIENCES > Chemistry > Applied Chemistry
Divisions:	Division of Physical Chemistry
Depositing User:	Borislav Kovačević
Date Deposited:	27 Jan 2026 09:07
URI:	http://fulir.irb.hr/id/eprint/11153
DOI:	10.1016/j.bioorg.2023.106965

Actions (login required)

View Item