0618286 - ÚFCH JH 2026 RIV NL eng J - Journal Article
Wloch, A. - Sengupta, P. - Szulc, N. - Kral, T. - Pawlak, A. - Henklewska, M. - Pruchnik, H. - Sýkora, Jan - Hof, Martin - Gladkowski, W.
Biophysical and molecular interactions of enantiomeric piperonal-derived trans β-aryl-δ-iodo-γ-lactones with cancer cell membranes, protein and DNA: Implications for anticancer activity.
International Journal of Biological Macromolecules. Roč. 303, APR 2025 (2025), č. článku 140476. ISSN 0141-8130. E-ISSN 1879-0003
R&D Projects: GA ČR(CZ) GX19-26854X; GA ČR GA22-25953S; GA MŠMT EH22_008/0004558
Institutional support: RVO:61388955
Keywords : human serum-albumin * styryl-lactones * establishment * antitumor * fluidity * design * liposomes * analogs * drugs * Enantiomeric iodolactones * cancer cell membrane * hsa * dna * Single-molecule fluorescence spectroscopy
OECD category: Physical chemistry
Impact factor: 7.7, year: 2023 ; AIS: 0.969, rok: 2023
Method of publishing: Limited access
Result website:
https://www.sciencedirect.com/science/article/pii/S0141813025010256?via%3DihubDOI: https://doi.org/10.1016/j.ijbiomac.2025.140476

Developing novel anticancer agents requires understanding their interactions with biological systems at both the cellular and molecular levels. Enantiomeric lactones have demonstrated notable cytotoxic activities against various cancer cell lines. Building on this foundation, we investigated enantiomeric piperonal-derived trans beta-aryl-delta-iodo-gamma-lactones ((-)-(4S,5R,6S) and (+)-(4R,5S,6R)), focusing on their impact on cancer cells membrane (Jurkat and GL-1), model membranes, and biomacromolecules such as human serum albumin (HSA) and DNA. Also, the cytotoxicity toward red blood cells and the antitumor activity of the compounds were evaluated against a set of canine lymphoma and/or leukemia cell lines. Membrane interaction studies revealed that both enantiomers interact with the hydrophobic core of lipid bilayers, enhancing lipid acyl chain packing, with the (-)-(4S,5R,6S) isomer showing a stronger impact on membrane fluidity. Comprehensive spectroscopic and theoretical studies revealed distinct stereochemical differences in binding affinities to HSA, where the (-)-(4S,5R,6S) isomer showed higher binding affinity and significant hydrophobic interactions. Detailed biological studies demonstrated that both enantiomers exhibit antiproliferative and proapoptotic activities, with the (-)-(4S,5R,6S) enantiomer showing higher activity. This study underscores the biological activity and interactions of enantiomeric iodolactones derived from piperonal with biomacromolecules, providing comprehensive insights into their biophysical behavior and potential anticancer properties.
Permanent Link: https://hdl.handle.net/11104/0365129